Mam 


/ 

LIBRARY 

"  OF  THE 

UNIVERSITY  OF  CALIFORNIA. 


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Accession  No.    Q  0  Q $  ^. 


a 


THE    PRINCIPLES   OF 
BACTERIOLOGY 


OK    THK  ^      . 

TTNIV  CRSI.TY  ' 


\ 


PHAGOCYTOSIS  (AFTER  METSCHNIKOFF). 


THE  PRINCIPLES 


OF 


BACTERIOLOGY 


BY 

DR.  FERDINAND  HUEPPE 

PROFESSOR  OF   HYGIENE   IN  THE   UNIVERSITY  OF    PRAGUE 


| 

AUTHORIZED   TRANSLATION    FROM   THE    GERMAN 
BY 

DR.  E.  O.  JORDAN 

ASSISTANT   PROFESSOR   OF   BACTERIOLOGY    IN   THE   UNIVERSITY  OF  CHICAGO 


CHICAGO 
THE  OPEN  COURT  PUBLISHING  COMPANY 

LONDON:  KEGAN  PAUL,  TRENCH,  TRUBNER  &  Co. 
1899 


BIO  LOST 
LIBRARY 

a 


COPYRIGHT,  1899 

BY  THE  OPEN  COURT  PUBLISHING  COMPANY 
CHICAGO 

All  rights  reserved 


TRANSLATOR'S   NOTE 


In  the  translation  of  Prof.  Hueppe  s  book 
I  have  endeavored  simply  to  reproduce  the  author  s 
ideas  with  clearness  and  fidelity.  I  have  added 
some  footnotes  and  a  few  references  to  important 
and  classic  papers  and  to  lately  published  work 
of  interest,  without,  however,  any  pretension  to 
completeness.  In  the  main  the  book  is  presented 
as  it  came  from  the  hands  of  the  author. 

EDWIN  O.   JORDAN. 


PREFACE. 


BACTERIOLOGY  is  just  now  in  transition  from 
the  natural  history  stage  to  the  scientific.  The 
former  aspect  is  adequately  treated  in  some  good 
and  comprehensive  manuals  which  attempt 
to  bring  together  all  the  available  data,  and 
there  exist  also  some  good  short  text-books 
which  contain,  in  addition  to  an  exposition  of 
methods,  the  more  important  facts  of  the  sub- 
ject set  forth  with  especial  view  to  the  needs  of 
the  physician.  The  way  in  which  bacteriology 
originated  and  especially  the  mode  of  develop- 
ment of  methods  of  investigation  have  brought 
it  to  pass  that  the  natural  history  side  has  been 
kept  in  the  foreground  while  the  scientific  side 
has  been  relegated  almost  exclusively  to  the 
sections  dealing  with  protective  inoculations. 

This  mode  of  treatment,  however,  no  longer 
suffices  to  meet  a  growing  and  legitimate  de- 
mand. In  this  book  I  wish  to  present  an  at- 
tempt at  a  critical  and  comprehensive  expo- 
sition of  bacteriology  basing  it  clearly  and 
solidly  upon  scientific  conceptions.  I  make  this 


VI  PREFACE. 

essay  in  order  that  our  knowledge  of  the  causes 
of  putrefaction,  fermentation  and  disease,  to- 
gether with  the  methods  of  the  prevention  and 
cure  of  infection,  may  develop  in  a  way  free 
from  all  ontology.  It  is  sometimes  of  use 
to  restate  things  which  are  axiomatic.  The 
"  entities  "  or  u  essences,"  which  even  in  the 
age  which  has  discovered  the  law  of  the  con- 
servation of  energy  and  the  evolution  of  living 
things  by  means  of  the  struggle  for  existence, 
still  haunt  the  mind  of  the  physician  who  re- 
mains sunk  in  the  ontological  contemplation  of 
diseased  cells  and  disease-producing  bacteria, 
are  a  mere  remnant  of  priest  medicine  and  can 
have  no  place  in  any  scientific  conception  of 
biology,  pathology  or  hygiene. 

Without  trenching  in  any  way  upon  the  field 
of  works  which  aim  at  bringing  together  all 
the  material  at  our  disposal  or  at  the  special 
introduction  of  physicians  to  the  subject,  I  may 
be  permitted  to  hope  that  this  first  mechanical 
and  monistic  exposition  of  bacteriology  will 
be  welcomed  by  many  readers  as  a  comple- 
ment of  the  other  works,  and  that  it  will  com- 
mend itself  as  a  trustworthy  guide  to  all  who 
wish  to  make  themselves  acquainted  with  the 
present  standpoint  and  the  prospective  pro- 
gress of  scientific  bacteriology.  For  this  rea- 
son I  have  given  adequate  recognition  not  only 


^PREFACE.  vii 

to  the  point  of  view  of  the  physician,  but  to  that 
of  the  botanist,  the  general  biologist,  and  the 
chemist,  and  indeed  to  that  of  all  those  who 
have  a  general  interest  in  the  progress  of 
modern  science  and  who  wish  to  inform  them- 
selves upon  the  practically  important  questions 
of  the  day. 

Like  all  branches  of  theoretical  and  practical 
medicine,  bacteriology  owes  much  of  its  early 
advancement  to  the  leaders  of  the  Prussian 
army  medical  department.  The  Prussian  sur- 
geon Struck,  as  head  of  the  Imperial  Board 
of  Health  in  Berlin,  took  the  initiative  in  creat- 
ing the  first  standard  working  laboratory,  which 
served  as  a  model  for  all  subsequent  institutes  ; 
without  this  powerful  aid  Koch  could  not  have 
developed  his  pioneer  methods. 

Earlier  pupils  of  the  army  medical  school, 
like  Helmholtz,  Virchow,  Reichert,  Leyden, 
Fischer,  and  Nothnagel  had  already  achieved 
important  professional  positions  ;  and  upon  the 
establishment  of  hygienic  and  bacteriological 
laboratories  and  the  creation  of  professorships, 
German  army  physicians,  and  chiefly  indeed 
those  who  were  pupils  of  this  institute,  appeared 
as  workers  of  the  first  rank  ;  among  these  I  may 
name,  Bshring,  Buchner,  Fischer,  Gartner, 
Gaffky,  Loffier,  R.  Pfeiffer  and  Schroter.  I 
myself  also  have  the  honor  to  be  a  pupil  of  this 


Vlll  PREFACE. 

institution.  It  is  an  especial  pleasure  to  me, 
therefore,  in  grateful  remembrance  of  the  help 
that  I  received  from  Surgeons-General  Grimm 
and  v.  Coler,  the  present  honored  head  of  the 
Prussian  Army  Medical  School,  and  from  my 
former  chief,  Army  Surgeon  Struck,  to  dedicate 
this  work  to  the  famous  institution,  on  this  its 
centennial  anniversary. 

THE  AUTHOR. 

PRAGUE,  August  2,  1895. 


TABLE  OF  CONTENTS. 


CHAPTER  PAGE 

I.  THE  STRUCTURE  OF  BACTERIA i 

-  -  II.  THE  VITAL  PHENOMENA  OF  BACTERIA 50 

Anaerobiosis  ;   Relations  to  Energy 50 

Light  and  Temperature  ;   Sterilization 61 

Disinfection  ;   Effect  of  Poisons 71 

Chemistry  of  the  Nutrient  Substratum.   91 

Active  Proteids  ;   Ptomains  ;    Leucomains 1 18 

Effect  of  Bacteria  Upon  the  Substratum    125 

Practical  Applications 132 

Cycles  of  Activity  and  Adaptation 138 

III.  BRIEF   DESCRIPTIONS   OF  THE   MOST   IMPORTANT  PA- 

THOGENIC BACTERIA 146 

IV.  THE  CAUSE  OF  INFECTIOUS  DISEASE 220 

Causes  and  Their  Identity  and  Equivalence  With  Effects.  230 

Resistances  and  External  Conditions 232 

The  Liberation  of  Energy 234 

Atomic  Combinations  and  Resistances 237 

Predisposition  to  Disease:  Acquired  and  Inherited 242 

Disease-Stimuli 251 

Infection  and  Contagion 272 

V.  CAN  DISEASE  BE  CURED  BY  COMBATING  THE  CAUSE?  275 

VI.  IMMUNITY;  PROTECTIVE- INOCULATION  ;  CURATIVE  IN- 
OCULATION   295 

Isopathic  or  Specific   Inoculation  With  Living  Parasites ; 

Attenuation  of  Disease-Producing  Bacteria 300 

Inoculation  With   Metabolic  Products  ;    Protective  Sub- 
stances and   Poisons;  Immunity  Does  Not  Depend 

Upon  Habituation  to  Poison ...    305 

Proteids 312 

ix 


X  CONTENTS. 

CHAPTER  PAGE 

Protective  Serum  ;  Active  and  Passive  Immunity;  Tissue 

Immunity  and  Antitoxin  Immunity 316 

The  Nature  of  Antitoxin 327 

Do  the  Antitoxins  Bring  About  Specific  Immunity?....   332 

Anticipatory  Inoculations  ;  Specific  Curative  Inocula- 
tions ;  Specific  Serum  Therapy. .  341 

Phagocytes  and  Alexius  ;  Antitoxic  and  Bactericidal  Sub- 
stances in  the  Blood 357 

Are  There  Protective  and  Curative  Inoculations  that  Are 

Non-Specific  ? 377 

Protective  and  Curative  Inoculations  Without  the  Use  of 

Micro-Parasites  or  Their  Products 390 

VII.  THE  PREVENTION  OF   INFECTIOUS  DISEASE    BY   COM- 

BATING THE   CAUSE   OF  THE   DISEASE 398 

VIII.  THE  HISTORY  OF  BACTERIOLOGY 440 

BIBLIOGRAPHY 457 


THE   PRINCIPLES   OF 
BACTERIOLOGY. 


CHAPTER  I. 

THE  STRUCTURE  OF  BACTERIA. 

DURING  the  last  decade  the  science  of  bac- 
teriology has  become  one  of  the  most  prominent 
branches  of  the  tree  of  knowledge.  Words  of 
the  craft,  like  "  pure  culture,"  belong  as  much 
as  the  phrases  "  struggle  for  existence  "  and 
"  conservation  of  energy  "  to  those  scientific 
idioms  which  have  been  admitted  to  citizenship 
in  the  general  community  of  speech. 

The  organisms  known  as  bacteria  are  mem- 
bers of  the  lowest  group  of  the  plant  kingdom. 
They  would  in  themselves  arouse  hardly  more 
attention  than  some  of  the  algae,  slime-fungi, 
or  moulds,  were  it  not  for  the  supervention  of 
some  special  interest.  This  special  interest 
lies  in  the  fact  that  bacteria  are  those  organ- 
isms which  research  has  brought  into  relation 
with  the  questions  of  spontaneous  generation, 
fermentation  and  decay,  and  the  origin  of  dis- 


2  BACTERIOLOGY. 

ease.  It  was  consideration  of  the  most  im- 
portant questions  of  biology  and  pathology,  of 
science  and  of  medicine,  that  first  directed  atten- 
tion towards  bacteria.  But  these  subjects  have 
not  of  course  been  developed  exhaustively  by 
reference  to  bacteria  alone.  Small  organisms 
belonging  to  other  groups  of  the  plant  king- 
dom and  even  to  the  animal  kingdom  stand  in 
a  similar  relation  to  the  questions  involved  ; 
and  we  may  speak  with  greater  precision  of 
micro-biology,  indicating  by  that  term  a  vast 
territory  into  which  investigation  has  made 
only  an  excursion.  If  we  still  continue  to 
allot  to  bacteria  the  major  part  of  this  territory, 
we  are  justified  for  the  reason  that  bacteria  are 
the  organisms  whose  participation  in  impor- 
tant biological  phenomena  was  first  discov- 
ered, and  because,  owing  to  the  development  of 
special  methods  of  bacterial  investigation,  we 
at  present  possess  in  this  group  of  microbes  the 
most  favorable  material  for  research. 

In  this  chapter  we  shall  consider  questions  re- 
lating to  bacterial  structure.  The  points  which 
are  of  the  greatest  general  interest  are  those 
bearing  upon  the  constancy  and  variability 
of  form,  and  upon  the  cellular  structure  which 
is  especially  interesting  because  these  organ- 
isms are  ordinarily  regarded  as  the  lowest  in 
the  scale  of  life. 


THE    STRUCTURE    OF   BACTERIA.  3 

In  the  simplest  and  smallest  of  living  things, 
visible  only  with  the  aid  of  the  microscope,  the 
entire  body  consists  of  a  single  cell.  The 
bodies  of  all  the  larger  and  higher  forms  of 
life  are  built  up  out  of  structural  units  similar 
to  these  independent  cell-organisms.  All  cells 
are  essentially  minute  masses  of  a  substance 
called  protoplasm,  a  semi-solid,  gelatinous  sub- 
stance which,  viewed  with  the  ordinary  micro- 
scope, is  apparently  homogeneous,  but  which, 
according  to  Altmann,  consists  of  small 
granules  of  an  albuminous  nature,  embedded 
in  a  similar,  structureless  albuminous  matrix. 
These  elementary  granules  or  granula,  are 
often  arranged  in  threads,  sometimes  in  such 
a  way  as  to  form  a  sponge-like  network  or 
reticulum ;  Butschli,  however,  regards  proto- 
plasm as  essentially  a  liquid,  possessed  of  a 
foam-like  or  "  honeycomb  "  structure.  On  Alt- 
mann's  view,  the  "  granule  "  is  the  vital  unit,, 
and  a  cell  in  its  simplest  form  is  to  be  regarded 
as  a  colony  of  such  "  elementary  granules  " 
rather  than  as  a  true  physiological  and  mor- 
phological unit.  But,  as  a  matter  of  fact,  the 
cell  is  the  simplest  and  lowest  form  of  living 
thing  now  known,  a  true  "  elementary  organ- 
ism "  (Briicke)  or  "  seat  of  life "  (Virchow). 
Growth  and  reproduction,  which  we  recognize 
as  conspicuous  phenomena  of  life,  are  always 


4  BACTERIOLOGY. 

met  with  in  the  cell ;  while  it  must  be  admitted 
that  at  the  present  time  we  can  only  in  a  limited 
sense  regard  the  granules  composing  the  cell 
as  endowed  with  the  peculiar  properties  of  life. 
If  there  exist  cells  composed  solely  of  proto- 
plasm (Monera,  Haeckel),  which  contain,  that 
is,  only  the  "  granules,"  or  the  threads,  mesh- 
work,  or  froth  constructed  out  of  these  par- 
ticles, such  cells  theoretically  would  be  the 
least  differentiated,  and  might  be  regarded  as 
those  from  which  the  higher  forms  have  been 
developed.  It  was  supposed  for  a  time  that 
free  cells  of  this  kind,  consisting  wholly  of  pure 
protoplasm,  existed  in  the  form  of  Haeckel's 
"  Urschleim"  but  the  existence  of  such  struc- 
tures has  not  been  confirmed. 

Bodies  which  are  undoubted  cells  all  show 
some  degree  of  differentiation.  Indeed,  animal 
cells  always,  and  plant  cells  almost  always,  con- 
tain a  definite  rounded  body  called  the  nucleus. 
Only  some  of  the  lowest  plant  cells  appear  to 
be  devoid  of  a  nucleus.  Many  cells,  especially 
plant  cells,  are  surrounded  by  a  dense  wall  or 
cell-membrane.  Many  cells  also  contain  vac- 
uoles,-  either  true  cavities  or  cavities  filled  with 
fluid  ;  and  frequently  granules  other  than  pro- 
toplasm are  found  associated  with  the  cell-sub- 
stance, the  name  paraplasm  or  deutoplasm 
being  given  to  these  particles.  These  mor- 


THE   STRUCTURE    OF   BACTERIA.  5 

pliological  elements  of  the  cells  are  in  fact 
primitive  organs.  The  nucleus  seems  to  be 
specially  concerned  in  the  division  and  repro- 
duction of  the  cell ;  the  membrane  serves 
partly  as  a  means  of  protection,  but  also  in- 
fluences reproduction  in  so  far  as  it  limits  the 
size  of  the  cell  and  modifies  nutrition  ;  the 
paraplasm  consists  of  food-material,  reserve 
substances,  secretions  and  the  various  meta- 
bolic products  ;  the  vacuoles  assist  in  the  diges- 
tion and  distribution  of  nutrient  substances  ; 
while  the  protoplasm,  in  a  more  precise  sense, 
attends  to  respiration  and  assimilation.  The 
protoplasm  possesses  also  the  property  of  con- 
tractility, and,  in  consequence,  has  the  power 
of  changing  its  place  or  moving  about. 

Bacteria  were  regarded  by  Ehrenberg  (1838) 
as  very  complicated  "  infusion-animals,"  while 
later  they  came  to  be  looked  upon  as  quite 
simple  vegetal  organisms  consisting  merely  of  • 
protoplasm  and  a  membrane.  At  present  we 
halt  midway  between  the  conception  of  great 
simplicity  in  organization  and  that  of  great 
complexity.  The  bacterial  cell  consists  of 
finely  granular  protoplasm,  which  in  the  small- 
est forms  is  apparently  homogeneous,  and 
which,  according  to  Alfred  Fischer,  behaves 
toward  reagents  like  plant  protoplasm.  In 
the  cell-body  there  are  sometimes  to  be  seen 


6  BACTERIOLOGY.    ' 

so-called  paraplastic  granules  of  an  oily  or  of  a 
starchy  character,  grains  of  sulphur,  and  at 
times  vacuoles.  The  cell-membrane  has  been 
long  known  and  the  fact  of  its  existence  se- 
curely established.  It  consists  in  some  in- 
stances of  a  substance  physically  altered,  but 
akin  to  protoplasm,  and  is  of  a  proteid  nature, 
thereby  resembling  the  membrane  of  animal 
cells.  Some  species,  however,  possess  a  cellu- 
lose-like membrane  resembling  that  of  the 
typical  plant  cell. 

Many  years  ago  I  was  able  to  show  that  dur- 
ing the  division  of  bacteria  there  occurred  a 
very  remarkable  arrangement  of  the  granules 
made  visible  by  staining,  which  is  similar  to 
that  taking  place  in  the  division  of  the  nu- 
clear filaments  of  higher  cells.  The  manner  in 
which  the  general  bacterial  substance  stains  is 
also  suggestive  of  nuclear  and  not  of  cytoplas- 
mic  reaction.  Biitschli l  definitely  conceives  the 
whole  central  part  of  the  cell  to  be  the  nucleus  ; 
according  to  this  conception,  the  smallest  bac- 
teria would  possess  hardly  more  than  a  mantle 
of  cytoplasm  and  often  would  consist  entirely  of 
nuclear  substance.  More  often  it  is  possible  to 
detect  the  presence  of  granules  which  react  like 
nuclear  substance,  and  which  must,  therefore, 

1  Cf.  Weitere  Ausfuhrungen  iiber  den  Bau  der  Cyanophyceen  und 
Bakterien,  Leipzig,  1896. 


THE   STRUCTURE   OF   BACTERIA. 
1.  2. 


Fig.  1.— The  Structure  of  Bacteria  (after  Blitschli). 

1-5  correspond  to  about  2000-2500  linear  magnification, 
i.  A,  Chromatiiun  Okcnii  in  optical  longitudinal  section  ;  B, 
in  optical  cross-section.  Killed  with  alcohol  and  stained  with 
hsematpxylin  after  the  bacterio-purpurin  and  sulphur  grains  have, 
been  dissolved  out.  The  reticular  appearance  is  regarded  as  the 
optical  expression  of  a  foam-like  structure  :  the  central  body,  c,  is 
more  compact  than  the  peripheral  layer  b;  the  thickenings  at 
a  accord  with  the  view  of  a  foam  structure.  While  the  reticu- 
lum  itself  stains  with  the  blue  color  of  alkaline  haematoxylin,  the 
granules,  a,  give  the  violet-red  color  of  acid  haematoxylin  ;  with 
methylene  blue  also  the  granules  stain  red,  the  reticiilum  blue. 
According  to  Biitschli  the  central  body,  c,  is  the  nucleus,  the 


8  BACTERIOLOGY. 

peripheral  layer,  b,  the  mantle  of  cytoplasm,  the  red  granules,  e, 
are  chromatin  grains  and  the  blue  reticulum  is  linin. 

2.  Spirillum  undula   in  process   of  division.    The  nucleus,  c, 
lies  next  to  the  membrane  ;  the  cytoplasm,  b,  occupies  a  rela- 
tively small  part  of  the  cell  and  is  found  at  the  poles  and  in  the 
middle. 

3.  A  bacterium  found  in  stagnant  water  ;  the  cell  is  almost 
wholly  nuclear  substance,  c,  and  the  cytoplasm,  b,  is  confined 
to  a  small  amount  at  one  pole. 

4.  Cladothrix   dichotoma  ;  portion  of  filament, /=sheath. 

5.  Chromatium  Okenii  in  conjugation  (after  F.  Forster),  s  = 
sulphur  grains  ;  ^  =  the  channel  of  connection  between  the  con- 
jugating cells. 

o.  a  and  ft,  Chromatium  Okenii ;  c,  B.  lineola  (after  a  photo- 
graph) ;  linear  magnification  about  900. 

be  regarded  as  undeveloped  nuclei.  (Fig.  i.) 
Ernst  was  the  first  to  observe  these  granules 
which  stained  red  and  not  blue  with  methylene 
blue.  A.  Fischer z  has,  however,  recently  main- 
tained that  this  coloration  was  due  not  to  a 
chemical  peculiarity,  but  to  physical  conditions. 
In  his  opinion  the  substance  of  a  bacterial  cell, 
in  spite  of  the  fact  that  it  stains  after  the  man- 
ner of  nuclear  substance,  behaves  on  the  whole 
like  the  cytoplasm  of  a  plant  cell.  When  it  is 
plasmolyzed  by  strong  salt  solution,  alcohol  or 
heat,  it  adheres  to  the  cell  wall  and  breaks  up 
into  irregular  masses  or  even  at  times  into 
masses  so  regular  as  to  present  the  appear- 
ance of  "  central  bodies "  or  polar  granules 
(Fig.  2).  The  "  central  body  "  of  Butschli  is 
therefore  considered  by  Fischer  as  merely 
plasmolyzed  cytoplasm.  Whatever  be  the 
truth  of  the  matter,  the  bacterial  cell  is  cer- 
tainly not  the  simplest  form  of  cell  that  may 

1  Ueber  den  Ban  cler  Cyanophyceen  und  Bakterien,  Jena,  1897. 


THE    STRUCTURE    OF   BACTERIA. 


1. 


3. 


Fig.  2.— The  Structure  ot  Bacteria  (after  Alfred  Fischer). 
Appearances  obtained  by  plasmolysis. 
1-3  enlarged  I  :  1500. 

1.  The  comma  bacilli  of  Finkler  and  Prior,  plasmolyzed  with 
5  p.  c.  NaCl  solution,  showing  contraction  of  the  cell  contents — 
the  nucleus  according  to  Butschli— into  a  and  b,  and  finally  the 
breaking  up  into  c,  two  polar  granules. 

2.  Leptothrix  buccahs  after  treatment  with  10  p.  c.  nitric  acid  ; 
the  membrane  is  more  translucent  than  the  contracted  and  dis- 
integrated cell  contents. 

3.  Clostridium  butyricum  treated  with  5  p.  c.  NaCl  solution. 


10  BACTERIOLOGY. 

4-7.  Spirillum  undula  treated  by  the  method  of  drying,  and 
staining  with  aniline  dyes  ;  in  the  different  stages  of  division 
and  in  different  individuals  the  cell  contents  (Biitschli's  "central 
body  "  or  "  nucleus  ")  contract  in  various  ways  :  6  alone  shows 
a  sort  of  division  into  two  new  central  bodies  that  accords  with 
Biitschli's  interpretation.  In  all  the  figures  the  cell  substance  is 
dark,  the  cell  wall,  which  is  left  free  by  the  contraction  of  the 
contents,  is  clearer  and  is  faintly  stained  in  the  process  of  stain-- 
ing the  flagella  ;  the  outer  Jayer,  however,  is  not  a  mantle  oi 
cytoplasm  as  supposed  by  Biitschli. 

be  conceived  to  exist,  and  in  this  connection  it 
is  safe  to  claim  only  that  it  is  the  lowest  cell 
form  that  can  without  question  be  regarded 
as  a  plant.1  Since  we  know  certain  unicell- 
ular organisms  whose  relations  to  the  plant 
and  animal  kingdoms  are  doubtful,  bacteria 
are  probably  not  the  most  rudimentary  form 
of  cell. 

In  the  early  studies  of  bacterial  forms  certain 
kinds  with  marked  characteristics  were  found  in 
connection  with  various  specific  diseases  and 
specific  decompositions.  These  could  be  distin- 
guished from  one  another  with  such  ease  that 
particular  stress  was  laid  upon  the  description 
of  such  typical,  "regulation  "  forms.  It  came 
to,  be  recognized  later,  however,  that  these  dif- 
ferent cell-forms  are  linked  together  by  all  pos- 
sible intermediate  stages.  In  order  to  permit 
of  a  rapid  orientation  it  has,  therefore,  become 
the  general  practice  to  enumerate  only  three 
chief  form  groups  : 

1  Perty  and  F.  Cohn  were  the  first  to  recognize  the  affinity  of  these 
organisms  to  the  plant  kingdom. 


THE   STRUCTURE   OF   BACTERIA,  II 

a.  Coccus-forms,  comprising  spherical   and 
ellipsoid  cells. 

b.  Rod-shaped  forms,  plainly  elongated  in 
one   direction.     These  may  be   distinguished 
according  to  their  length  as  long  or  short  rods. 
Many   rods  have  an    approximately    uniform 
diameter   throughout    and  the    ends    may   be 
either  rectangular  in  outline  or  more  or  less 
rounded.     In  some  rods  the  diameter  of  the 
cell    varies    in     different    portions    so    as    to 
produce  a  spindle-shaped  or  club-shaped  cell, 
or  one  fashioned  like  a  pestle,  or  a  whetstone 
or  a  drumstick.     Rods  may  be  rigid  or  flexi- 
ble, and,  in  the  latter  case,  often  appear  curved. 

c.  Corkscrew  forms,  comprising  all  spirally 
twisted  cells.     The  smallest  forms  often  resem- 
ble rods  bent  with  a  comma-like  flexure.     The 
screws  may  be  rigid  or  flexible,  of  equal  diam- 
eter throughout,  or  varying  in  diameter  at  dif- 
ferent points. 

Each  bacterial  cell  is  able  to  maintain  an 
independent  existence,  and  frequently  exhibits 
transition  forms  in  the  course  of  its  own 
development.  A  sphere  elongates  into  an 
ellipsoid  ;  a  long  rod  stretches  out,  divides  and 
becomes  two  short  rods  ;  a  short  rod  or  spiral 
divides  into  two  ellipsoids  or  spheres.  Before 
division,  the  individual  cells  as  a  rule  elongate, 
and  their  forms  become  thereby  more  clearly 


12  BACTERIOLOGY. 

defined.  Conversely,  the  young  daughter  cells 
are  smaller  and  consequently  less  distinct 
(Fig.  3).  The  value,  then,  of  the  individual 
shapes  fluctuates  very  greatly.  At  times  it  is 
the  transitory  division  form,  at  times  the  com- 


Fig 3.— Bacterium  Zopfii  (after  Kurth).  A,  Short  rods  in  process 
of  division  into  arthrospores,  d.  B,  Longer  rods.  C,  Curved 
threads  or  filaments,  in  part  segmented.  Z),  Straight  filaments 
in  part  segmented.  E  and  F,  Twisted  filaments  and  coils.  G 
and  H,  Spiral  forms.  /,  Germination  of  the  arthrospores. 

mon  mature  form  that  is  deemed  "  typical." 
Only  as  applied  to  the  mature  forms  does  the 
above  grouping  hold  good.  On  this  account  it 
is  superfluous,  at  least  in  the  beginning,  to  de- 
termine with  rule  and  compass  the  "  regula- 
tion "  length  or  breadth  of  a  species,  while  gen- 
eral morphological  questions  remain  unsettled 
which  are  plainly  of  more  consequence. 

It  must  be  remarked  furthermore  that  even 


THE  STRUCTURE  OF  BACTERIA.        13 

the  typical  forms  recur  only  under  quite  defi- 
nite conditions  and  that  they  vary  according 
to  the  nutrient  media  in  which  the  bacteria 
are  growing.  This  holds  true,  indeed,  to  such 
an  extent  that  the  prevailing  form  of  a  given 
species  must  be  assigned  to  one  group  or  an- 
other, according  as  it  has  been  taken  from  one 
or  another  medium.  In  this  way  bacteria 
have  been  shifted  from  one  class  to  another,  as 
for  example  is  the  case  with  the  "  miracle 
germ  "  which,  in  accord  with  its  common 
form,  was  originally  placed  among  the  spher- 
ical bacteria,  but  has  been  removed  under  the 
bacteriological  regime  to  the  group  of  rod  bac- 
teria ;  in  truth,  it  may  be  rightly  placed  in 
either  group. 

After  division  the  single  cells  may  remain  in 
more  or  less  intimate  union  (Fig.  4).  The  in- 
dividual members  of  this  association  may  either 
preserve  an  independent  existence,  so  that  the 
association  is  simply  a  loose  aggregation  of 
cells,  or  the  union  may  be  so  close  that  the 
group  of  cells  appears  to  form  an  organic  unit. 

A.  If  division  takes  place  in  a  single  plane, 
chains  and  filaments  of  cells  arise  ;  the  members 
of  the  chain  may  be  sharply  defined  one  from 
another  or  may  be  without  apparent  boundary. 
In  the  latter  case  long  filaments  are  formed 
which,  from  their  possession  of  an  outer 


BACTERIOLOGY. 


Jt> 


Fig.  4.— Groupings  of  bacteria  found  in  the  larger  zoOglceae.  A 
Single  layered  tetrads.  B,  Development  of  the  tetrads,  a,  b,  c 
into  the  packets,  d,  e,  the  cubical  arrangements  of  cells  being 
shown  in  d,  but  not  in  e.  C,  Coccus-forms  with  capsules.  D, 
Development  of  rods  and  subsequent  breaking  up  of  these  into 
cocci  inside  of  a  capsule  (Friedlander's  Pneumobacillus).  E-H, 
Leuconostoc.  E,  Arthrospores  and  F,  their  germination,  and 
H,  their  reformation.  J  and  K,  Spiral  forms  in  gelatinous  en- 
velopes or  capsules,  formerly  described  as  the  genus  My- 
conostoc. 

sheath  and  by  their  true  branching,  betray  an 
affinity  to  the  fission-algae  (Fig.'  5).  Both 
threads  and  filaments  may  according  to  the 
rigidity  of  the  membrane  be  motile  or  non- 
motile,  straight  or  wavy  in  outline,  or  spirally 
twisted.  The  spiral  threads  are  closely  or 
loosely  wound,  stiff  or  yielding.  At  times  a 
single  filament  may  be  found  straight,  curved 
and  spirally  twisted,  at  different  points.  It 
sometimes  happens  that  motile  filaments  form 
loops,  or  roll  up  into  coils,  or  wind  around  one 
another  like  whiplashes.  Certain  kinds  show 
a  distinction  between  base  and  apex. 

It  is  often  difficult  at  first  sight  to  determine 


THE   STRUCTURE   OF   BACTERIA. 


Fig.  S—Cladothrix  dichotoma  (after  Zopf)  A,  Branched  filament  with 
spiral  branches  more  (b)  or  less  (a)  twisted.  B,  Screw  forms 
one  end  of  which  (a)  is  more  twisted  than  the  other.  C,  Long 
spirochaete-like  branch  with  numerous  coils  and  twists.  D,  a 
piece  of  a  branch  with  sharp  angled  spirals,  and  one  with  very 
slight  turns.  E,  Screw  forms  :  a,  unsegmented,  b,  with  the  ap- 
pearance of  segmentation  into  longer  and  c,  into  shorter  seg- 
ments. F,  Spirochaete  forms  :  a,  unsegmented,  b-d,  schematic 
representation  of  segmentation,  6,  into  long,  c,  into  short  rods 
and  d,  into  cocci. 

whether  the  form  under  observation  is  merely 
a  chain  of  single  rod-like  or  spiral  cells,  or  is  a 


1 6  BACTERIOLOGY. 

real  filamentous  species,  and  whether  the  in- 
dividual elements  in  the  association  are  large 
or  small.  Early  observers  indeed,  especially 
Ehrenberg  and  Naegeli,  fell  into  the  error  of 
assuming  that  there  is  really  only  one  funda- 
mental form,  the  coccus,  out  of  which  by  vari- 
ous combinations  all  the  other  forms  can  be 
derived. 

B.  Growth  can   occur  also   in    two  dimen- 
sions so  that  flat  sheets  of  cells  are  formed. 
If  growth  takes   place  by  cross-division,  then 
groups  of  four  cells,  tetrads   or  tablet-forms, 
result.      If   division  is    longitudinal    in    rods 
which  remain  in  contact  at  one  point,  a  radiat- 
ing structure  is  produced  (Fig.  6). 

C.  By  division  of  the  cells  in  all  three  di- 
mensions, cubical  masses  or  packets  like  bales 
of  merchandise  are  formed.     These  are  the  so- 
called  Sarcincz  (Fig.  7). 

D.  Finally  there  may  arise  wholly  irregu- 
lar groups  or  heaps  which   have   a   spherical, 
lobed  or  botryoidal   appearance.     To   such  ir- 
regular   cell-clusters    names   like    Ascococcus, 
Staphylococcus,    Clathrocystis,    Zobglcea    rami- 

gera,  etc.,  have  been  applied  (Fig.  8).  Indi- 
vidual cells  may  be  grouped  and  united  in  dif- 
ferent ways  in  one  and  the  same  species  under 
varying  conditions  of  life. 

Among  the  rod-shaped  organisms  especially 


THE    STRUCTURE   OF   BACTERIA.  I? 


t      f      f      f 


11  12 

Fig.  6. — Pasteuria  ramosa  (after  Metschnikoff). 

1-4.  Stages  of  the  longitudinal  division  showing  the  resulting 
ray-like  arrangement  of  cells. 

5-12.  Formation  of  endospores  (after  drawings).  Magnified 
about  i  :  2000. 

it  has  been  observed  that  during  the  course  of 
development  straight  rods  sometimes  undergo 
a  thickening  in  the  middle  of  the  cell,  thus  be- 
coming spindle-shaped,  or  at  the  end,  causing 
a  club-shaped  appearance.  In  some  cases 
these  enlarged  bacilli  seem  to  be  forms  especi- 
ally concerned  in  the  production  of  fermenta- 


1 8  BACTERIOLOGY. 

tion,  as  Hansen  I  has  observed  to  be  the  case 
with  the  acetic  acid  bacteria,  and  Hueppe  with 

A.  B. 


C. 


Fig.  7.— A.  Sarcince  from  the  stomach  (after  DeBary),  fresh,  un- 
stained.    Drawings  magnified  i  :  600. 

B.  Sarcina  minnta  (De  Bary).     i,  cocci,  2,  division  into  diplo- 
cocci,  3,  single-layered  tetrads  or  merista  forms,  4  and  5,  forma- 
tion of  packets. 

C.  Sarcince  from  the  lung,  double-stained  preparation  show- 
ing endospores  ;  the  dark  portions  are  the  (red)  spores  either 
in  the  (blue)  cells  or  isolated. 


A 


Fig.  8.—  Ascococcus  (after  F.  Cohn),  enlarged  65  times,  showing, 
inside  the  gelatinous  colony,  segmentation  into  small  (a)  and 
large  (b)  spherical  colonies  of  cocci  which  appear  to  lie  in  cham- 
bers. B,  The  Clathrocystis  form  of  Beggiatoa  rosco-persicina 
(after  Zopf) ;  the  large  chromatia  (monads  of  earlier  authors) 
just  visible  ;  magnified  i  :  250. 

the  bacteria  which  produce  propionic  acid.     In 
the  latter  instance  these  irregular  forms  appear 

!Ber.  d.  Deutsch  Bot.  Ges.,  1893. 


THE    STRUCTURE    OF   BACTERIA.  19 

when  fermentation  is  at  its  height.  In  such 
cases  they  may  be  regarded  as  true  develop- 
mental forms.  In  other  species  such  an  ap- 
pearance foreshadows  spore-formation.  Even 


Fig.  9. — Degeneration  forms.  J,  lactic  acid  bacteria  after  Maddox. 
B,  Clpstridium  polymyxa,  after  Pra/mowski.  C.  Bacterium 
Zopfii,  after  Kurth.  D,  B.  Snbtilis  and  E,  B.  anthracis,  after 
BLichner.  F,  Vibrio  nigula,  after  Warming.  G,  V.  cholerce 
asiaticce,  after  van  Ermenghem  and  Hueppe. 


more  frequently  such  forms  appear  as  the 
forerunners  of  death, — as  degeneration  forms 
due  to  the  swelling  up  of  the  membrane  (Fig. 
9).  Death  is  also  sometimes  accompanied  by 


20  BACTERIOLOGY. 

granular    disintegration    of  the    cell-contents 

(Fig.  10). 

If   the  outer  cell-membrane  swells  up  and 

becomes  gelatinous,  an  envelope  or  capsule  is 

formed.     The  gelatinous  scum  or  zooglcea  that 

spreads  over  the  sur- 
face of  decomposing 
fluids  is  composed  of 
^  ..     such  a   film  of  bac- 

teria held  together 
by  their  gelatinous 
envelopes.  Ins  i  d  e 

the    mass  an  order- 
Fig.  10. — Granular    disintegration  of  ^  ., 

bacteria,    4v.supposed  typica  dis-  ly    arrangement    of 

integration  of  a  spirochiete  from        11 

swamp -water,  first   into  longer,  Cell  groups    may  CX- 

then  into  shorter,  rods,  and  finally  .    t  T\   11  •    1 

into  little  spheres  (after  Zopf).    B,  ISt.  Pellicles    may 

ordinary  breaking  up   into  seg-  i  r               i                 ,  1 

ments,  and  C,  granular   disinte-  be  tormed     OU     the 

gration  of  comma  bacilli  (after           <•  r    n     •  i          i 

Hueppe).  surface  or  fluid  and 

solid      media,     and 

these  may  be  thin  or  thick,  smooth  or  corru- 
gated ;  in  the  interior  of  fluids  the  growth  may 
be  globular,  ramifying  or  in  grape-like  clus- 
ters. The  zooglcese  or  colonies  upon  certain 
solid  nutrient  media  like  gelatin,  agar-agar 
and  potato  are  especially  characteristic  (Fig. 
n).  The  shape  of  the  colony  and  the  kind  of 
development  vary  according  to  the  chemical  and 
physical  conditions  that  affect  nutrition  but 
under  similar  conditions  are  always  approxi- 


THE   STRUCTURE   OF   BACTERIA. 


21 


Fig.  ii.— Zooglcea  of  a  rodlike  form  found  in  the  bulbae  of  pem- 
phigus acutus  (after  Demme).    Agar  culture,  natural  size. 

mately  the  same,  so  that  the  morphological 
characters  of  a  colony  can  be  advantageously 
used  in  the  recognition  of  bacterial  species. 

One  of  the  greatest  services  that  Koch  has 
rendered  to  bacteriology  is  his  invention  of 
methods  of  pnre  culture,  by  means  of  which 
such  isolated  colonies,  originating  from  a  single 
germ,  can  be  cultivated  at  will  and  obtained 
free  from  any  admixture  with  germs  of  other 
kinds.  Such  pure  cultures,  reared  under  per- 
fectly similar  conditions,  always  agree  in  form 
and  physiological  action  at  any  given  stage. 
But  this  is  not  real  constancy.  The  similarity 
does  not  depend  upon  the  invariability  of  the 


22  BACTERIOLOGY. 

bacteria,  but  upon  the  fact  that  the  conditions  of 
life  suffer  no  alteration.  If  the  conditions  fluc- 
tuate, the  bacteria  will  also  vary  in  form  and  in 
physiological  activity.  Individual  bacteria  as 
well  as  their  zooglceae  or  colonies  always  adapt 
themselves  to  the  "  milieu"  The  constancy 
which  Koch's  method  revealed  was  not  one  of 
true  permanence  of  species,  but  rather  one  of 
permanence  of  varieties  due  to  station.  As 
one  emigrant  in  his  new  home  clings  strenu- 
ously to  the  manners  and  customs  of  his 
fatherland  while  another  quickly  forsakes 
them,  so  some  species  of  bacteria  transplanted 
into  changed  conditions  of  life  preserve  their 
original  characteristics,  while  others  part  with 
them.  It  is  possible  by  means  of  pure  cul- 
ture to  obtain  proof  of  the  validity  of  the  prin- 
ciple formulated  by  L.  v.  Buch  and  Moritz 
Wagner,  who  maintained  that  by  subjecting 
individuals  to  different  conditions  of  life,  new 
species  might  be  produced. 

Bacteria  can  be  separated  readily  into  genera 
and  species,  although  earlier  observers  as- 
sumed, that  these  organisms  possessed  an 
almost  limitless  variability  of  form  and  of 
physiological  activity.  There  are  certainly 
some  species  which  pass  through  compara- 
tively few  forms,  although  others  are  protean. 
Of  a  kindred  order  of  facts  is  the  observation 


THE   STRUCTURE   OF   BACTERIA.  23 

that  individual  forms  are  at  times  tolerably 
constant,  but  frequently  change  somewhat 
under  changing  external  conditions.  The  ex- 
istence of  rigid  form-species,  which  not  only 
the  earlier  observers,  but  even  Cohn,  Schroter 
and  Koch  assumed,  can  be  upheld  no  longer. 
The  adaptability  of  bacterial  forms  to  changing 
conditions  of  nutrition  is  not  so  boundless  as 
Naegeli  and  Billroth  supposed,  but  it  is  con- 
siderably greater  than  was  once  held  to  be  com- 
patible with  the  conception  of  the  existence  of 
constant  species. 

In  the  first  instance  form-species  or  form- 
genera  were  recognized  and  these  were  named 
after  the  most  prominent  forms.  It  was  in 
accordance  with  this  tendency  that  Ferdinand 
Cohn,  turning  the  older  names  to  good  account, 
applied  the  generic  title  Micrococcus  to  the  coc- 
cus form,  Bacterium  to  the  short  rods,  Bacillus 
to  the  long  rods,  and  Vibrio,  SpirocJuete  and 
Spirillum  to  the  various  spiral  forms.  These 
designations  did  not  really  serve  to  distinguish 
a  single  species,  and  Naegeli  and  Koch  added 
more  confusion  to  a  matter  which  was  in  itself 
simple.  The  name  Bacillus  was  applied  by 
these  investigators  not  to  long  rods  but  to  a 
genus  or  species  whose  most"  essential  "  form 
was  a  long  rod.  What  else  characterized  it, 
whether  it  changed  its  form  or  whether  it  pro- 


24  BACTERIOLOGY. 

duced  spores,  were  in  the  first  instance  mat- 
ters that  were  regarded  with  indifference. 

In  order  to  determine  truly  natural  genera 
and  species,  more  must  be  known  than  the  sup- 
posed "  typical,"  "  constantly  recurring,"  or 
"  principal  "  forms.  Something  additional  has 
been  obtained  through  our  knowledge  of  flag- 
ella.  (Fig  12.)  Many  cells  without  membranes, 
such  as  amoebae,  have,  as  is  well  known,  the 
power  of  sending  out  protoplasmic  processes 
quite  at  will,  as  in  the  so-called  pseudopodia. 
The  term  cilium  or  flagellum  is  used  in  a  more 
restricted  sense  than  pseudopodium,  and  is  ap- 
plied to  the  delicate  threads  of  protoplasm  which 
are  extended  through  definite  openings  in  the 
cell  membrane  and  which  retain  a  connection 
with  the  cell-contents.  The  flagella  of  bacteria, 
which  were  discovered  by  Ehrenberg,  are  now 
known  to  be  appendages  of  the  membrane, 
and  their  connection  with  the  cell  proto- 
plasm has  not  been  accurately  determined ;  they 
seem,  however,  to  be  true  organs  of  locomotion. 
The  possession  of  cilia  brings  bacteria  into 
closer  -relation  with  the  groups  of  monads  and 
flagellates,  organisms  which  are  regarded  as  ani- 
mals. A.  Fischer  has  attempted  to  make  use 
of  the  flagella  for  purposes  of  diagnosis.  He 
lays  stress  upon  the  presence  or  absence  of  these 
structures,  and  their  occurrence  singly  or  in 


THE   STRUCTURE   OF   BACTERIA.  25 

1.  2. 


B.  termo ;  3,  Cholera  bacteria.    4,  Typhoid 
bacteria  showing  rolling  up  of  flagella  (a) 


Fig.  12.— Flagella. 

I,  B.  subtilis ;  2, 

free  flagella,'  partly 

(b)  and  wholly  (c)  coiled.  "  1-4  enlarged  about  1500  diameters 
(after  A.  Fischer).  5, 6,  Proteus  vulgans  after  micro-photographs 
by  Fraenkel  and  Pfeiffer  ;  1500  diameters.  7,  Swine  plague 
bacillus.  8,  Potato  bacillus.  9,  Spirillum  scrpcns  after  micro- 
photograph  by  Neuhauss  (i  :  1000). 


26  BACTERIOLOGY. 

tufts  at  the  cell  poles,  or  distributed  over  the 
whole  cell  body.  Such  emphasis  is  provisional, 
indeed  premature,  since  little  is  yet  known 
about  the  conditions  of  cilia  formation.  M.  pro- 
digiosus,  for  example,  is  usually  non-motile,  but 
is  occasionally  motile  by  the  aid  of  flagella ; 
the  cholera  germ,  which  is  actively  motile  in 
ordinary  bouillon,  becomes  motionless  in  bouil- 
lon to  which  sugar  has  been  added. 

Par  more  important  as  an  aid  to  systematic 
classification  are  the  facts  afforded  by  spore-for- 
mation. In  multiplication  by  simple  division 
a  complete  rearrangement  of  the  cell-contents 
takes  place,  and  the  granules  in  the  protoplasm 
exhibit  a  much  more  definite  grouping.  At- 
tention has  been  called  elsewhere  to  this  obser- 
vation as  showing  an  analogy  with  the  arrange- 
ment of  nuclear  thread-work  during  mitotic 
division.  In  such  a  case  of  simple  cell  division, 
both  daughter  cells  serve  to  perpetuate  the 
species.  In  other  cases,  however,  this  method 
of  reproduction  does  not  suffice  for  the  preser- 
vation of  the  species  and  the  ordinary  vegetative 
cells  die  in  great  numbers  under  the  natural  or 
artificial  conditions  to  which  they  happen  to  be 
subjected,  such  as  light,  heat,  dryness,  chemi- 
cal influences  and  competition  with  microbes 
of  their  own  or  other  species.  In  this  event, 
certain  cells  that  are  more  resistant  take  charge 


THE   STRUCTURE   OF   BACTERIA.  2? 

of  the  perpetuation  of  the  species  under  the 
guise  of  a  resting-stage  or  spore.  Cohn  was  the 
first  to  observe  that  sometimes  the  single  cells 
that  become  detached  from  a  filamentous  bac- 
terium or  that  are  set  free  by  the  breaking  up 
of  the  filament,  do  not  possess  the  character  of 
ordinary  vegetative  cells  but  rather  resemble 
the  gonidia,  conidia  or  spores  such  as  are  found 
in  some  algae  or  moulds,  and  Hueppe  and  De 
Bary  subsequently  showed  that  in  many  bac- 
terial species  single  members  of  a  chain  may 
acquire  the  resistant  properties  and  the  func- 
tion of  the  resting-stage.  For  distinction  these 
were  called  arthrospores  (Figs.  3,  13,  19).  It 
appeared  in  some  instances  as  if  almost  any 
individual  cell,  while  not  unlike  the  others  in 
form,  might  under  certain  conditions  become  an 
arthrospore.  Hueppe  observed  that  such  a  cell 
would  sometimes  be  insulated  or  protected 
against  harmful  influences  by  a  mantle  of  the 
adjacent  dead  cells  formed  about  it.  In  other 
cases  the  arthrospores  increase  in  size  and  ac- 
quire a  compact  membrane,  as  happens  also 
in  some  algae.  In  some  leptothrix-forms  the 
gonidia  are  found  in  thickenings  of  the  sheath 
which  must  therefore  be  considered  as  the 
spore-bearer  or  sporangium. 

True  arthrospores  are  spheroidal  in  form,  but 
this  fact  must  not  lead  us  to  confound  them 


28 


BACTERIOLOGY. 


Fig.  13. — Gonidia  and  Arthrospores. 

A-E.  Crenothrix,  the  ends  of  the  filaments  are  the  places  where 
spores  are  formed — the  sporangia.  A  and  D,  macrogonidia  :  the 
segments  of  the  filament  are  undivided  or  broken  up  only  into 
quite  large  pieces  (A,  a).  B,  C,  E,  microgonidia  formed  by  re- 
peated division  and  subdivision  of  the  segments  :  after  expul- 
sion from  the  filament  zoogloea  forms  (C,  c  and  E,  c)  may  occur. 
These  microgonidia,  and  in  Beggiatoa  the  macrogonidia  also, 
may  at  times  develop  flagella  and  become  swarm  spores.  K,  the 
formation  of  arthrospores  in  rods  from  direct  observation  (Hu- 
the  previously  homogeneous  protoplasm  becomes  gran- 


ular (a),  contracts  (b),  divides  (c,  d,  et)  into  two  highly  refractive 
arthrospores,  each  of  which  is  surrounded  by  a  membrane  (e). 
F,  arthrospores  of  B.  Zofifii,  after  Kurth.  G,  Leuconostoc,  after 
van  Tieghem.  H  and  7,  comma  bacilli,  after  Hueppe  ;  these 
form  (J.  d,  e}  zooglceae  composed  of  coccus-like  arthrospores. 

with  the  polar  granules  produced  by  plasmol- 
ysis.  It  must  be  remembered  also  that  the 
gonidia  of  the  filamentous  bacteria  may  often 
form  zoogloeal  masses  of  coccus-like  forms. 
In  such  gonidia  flagella  have  been  sometimes 
observed,  showing  an  affinity  to  real  swarm- 
spores.  Coppen  Jones  T  has  recently  made  it 

1  Centralbl.  f.  Bakt.  xvii,  1895,  I- 


THE  STRUCTURE  OF  BACTERIA. 


29 


appear  probable  that  some  organisms  that  are 
generally  supposed  to  be  bacteria,  such  as  the 
so-called  tubercle  bacillus,  exhibit  a  type  of 
spore-formation  which  is  homologous  with  the 
chlamydospore  formation  of  true  moulds,  such 
as  Mucor  (Fig.  20). 

In  addition  to  the  true  bacteria,  or  to  those 
organisms  that  up  to  this  time  have  gone 
under  that  head,  which  propagate  by  arthro- 
spores  in  the  narrower  sense,  or  by  gonidia 
like  some  kinds  of  fission-algae,  or  by  chlarny- 
dospores  after  the  manner  of  some  kinds  of 
moulds,  there  are  some  bacteria  which  re- 
produce in  another  and  characteristic  fashion, 
namely  by  means  of  endogenous  spores  or 
endospores.  Endo- 
spores  were  discovered 
by  Pertyini852  (Fig. 
14).  It  is  necessary 
to  distinguish  two 

kinds       of       endospore-  Fig.  14.— The  endospores  of  bac- 
teria (first  seen  by  Perty). 


formation  which,  how- 
ever, are  connected 
with  one  another, 
through  intermediate 
forms.  In  bacteria  of 
the  first  and  more  comprehensive  type,  a  dark 
speck  appears  in  the  cell-contents  after — but 
sometimes  without — preliminary  granulation. 


A.  Sporonema  ;      belongs 
probably  to  the   swamp  bac- 
teria ;   shows    Klein's   second 
type  of  spore  formation. 

B.  Spirillum    undula,  per- 
haps the  same  as  Prazmow- 
ski's  Vibrio  rugula. 


BACTERIOLOGY. 


This    speck   becomes    gradually   larger   and 
reaches  its  ultimate  size  at  the  expense  of  the 


Fig  '15. — Endogenous  Spores  and  their  Manner  of  Formation. 

A,  in  the  first  type  the  previously  homogeneous  protoplasm 
becomes  granular  (a)  gathers  together  in  one  place  (b)  and 
finally  (c)  is  wholly  included  in  the  spore.  B,  C,  D,  true  bacilli 
in  which  spore  formation  occurs  without  altering  the  shape  of 
the  rod.  B,  B.  subtilis  ;  C,  anthrax  bacillus.  D,  B.  megathe- 
rium. E,  spindle-shaped  or  club-shaped  rods,  showing  changes 
of  form  preliminary  to  spore  formation.  In  E,  f,  only  one  of  two 
'  adjacent  cells  has  become  spindle-shaped.  In  g  it  appears  as 
if  two  spores  lay  in  a  single  cell  ;  as  a  rule,  however  (as  in  d), 
such  an  appearance  is  in  reality  due  to  a  close  connection  of 
two  cells.  E  are  forms  of  Clostridium  butyricum,  Cl.  polymyxa 
(partly  after  PrazmowskiX  F,  Plectridium  forms,  a,  Tetanus 
bacteria  ;  b  and  c,  Bacteria  from  putrefying  fluids.  G,  spore 
formation  in  the  genus  Vibrio  (V.  rugula)  after  Prazmowski. 
H,  endospores  in  Spirillum  after  van  Tieghem  ;  a,  b,  Spirillum 
amyliferum  ;  d,g,  Sp.  scrpcns  (?) 

cell-protoplasm.     In  a  colony  of  bacteria  differ- 
ent stages  of  spore-formation  may  be  simul- 


THE   STRUCTURE   OF   BACTERIA.  3! 

taneously  observed  (Figs.  6,  7,  15,  18).  By 
contraction  of  the  protoplasm  and  decrease  in 
the  quantity  of  water  contained,  the  spore 
comes  to  have  a  highly  refractive  appearance. 
Its  body  becomes  limited  externally  by  a  dense 
and  rapidly  formed 
spore-membrane.  The 
motile  forms  become 
motionless  before  spore- 
formation.  It  is  a  mat- 
ter of  secondary  signif- 
icance that  sometimes 
all  the  cell-protoplasm  r 

\        .   r  Fig.    16.— The    Germination    of 

is     converted     into     a       Spores. 

A,  B.  subtil  is   after  Bre- 

SpOre,     and      that     SOme  feld ;  the  spore  membrane 

.                             .                     .  splits  open  on  one  side,  the 

times  a  portion  remains  rod  grows,  however,  in  the 

.                     .  direction  of  the  long  axis  of 

OUtSlde.       It  IS    likewise  the   spore.     B,   Clostridinm 

.  butyricnm,  after    Prazmow- 

01      Subordinate      impor-  ski  ;  the  young  cell  grows 

from  the   pole.     In   the  en- 

tance  whether  the  Spore  dospores  A  and  B  the  empty 

..                     1  spore  membrane  is  left  be- 

be  round,  Oval    Or  bean-  hind  on  germination. 

.        .  C,  Gonidia  of  Leiiconostoc' 

Shaped,     whether     it      IS  after    van    Tieghem  ;    the 

£             j            .,             -1  11  membrane  of    the     arthro- 

lOrmed.  at  the  middle  OI  spore    a    becomes  swollen 

-i             11  and  the  arthrospore  grows 

the    Cell  Or    at  the     end,  like  a  vegetative  cell.    D,B. 

1       -             ,                ^  Zopfti   after    Kurth.     E. 

Whether    the       Cell     pre-  Commabacilli  after  Hueppe. 

serves  its  form  or  suffers  a  preliminary  swell- 
ing at  the  place  where  the  spore  is  to  form. 
In  the  germination  of  spores,  likewise,  similar 
small  and  inconsiderable  differences  make 
their  appearance  (Fig.  16).  These  characters 


BACTERIOLOGY. 


are  in  certain  cases  very  important  as  aids  to 
diagnosis,  but  are  not  so  essential  as  the  dif- 
ference shown  by  the  second  type  of  endospore 
discovered  by  Peters  and  L,.  Klein.1  In  this 


i. 


Fig.  17. — Endospore  formation  in  flagellate,  actively  motile  bac- 
teria ;  second  type  of  spore  formation  (according  to  Klein)  in 
bacteria  from  stagnant  water. 

1,  B.  Solmsii  with  protoplasm  disintegrated  by  plasmolysis  ; 
in  the  lighter  portions  the  protoplasm  is  drawn  away  and  the 
membrane  alone  shows. 

2,  B.  paludosum. 

3,  Clostridium  butyricum. 

.1-3  after  drawings  by  A.  Fischer,  about  i  :  2000. 

(Fig.  17),  there  is  an  initial  separation  of  the 
protoplasm  into  a  spore-forming  and  a  spore-free 
portion,  so  that  from  the  beginning  the  spores 

1  Ber.  d.  Deutsch.  Bot.  Ges.  1889,  vii-»  P-  57- 


THE   STRUCTURE   OF   BACTERIA.  33 

are  sketched  out  in  their  final  size  and  shape 
and  do  not,  as  in  the  first  type,  gradually  in- 
crease their  substance  at  the  expense  of  the 
rest  of  the  protoplasm.  During  the  process  of 
maturation,  the  nutrition  of  the  spore-rudiment 
is  provided  for  by  the  rest  of  the  cell-proto- 
plasm, and,  as  the  cilia  bear  witness,  the  move- 
ments of  these  species  do  not  cease  during 
spore-formation.  Endospores  are  most  com- 
mon among  the  rod-bacteria,  but  they  have  also 
been  positively  observed  in  coccus  and  spiral 
forms. 

Pasteur  succeeded  in  suppressing  spore-for- 
mation in  the  anthrax  bacillus  by  subject- 
ing it  to  a  temperature  of  between  42°  and 
43°.  Roux1  and  Phisalix2  obtained  a  similar 
result  by  the  addition  of  carbolic  acid  to  the 
culture  medium,  a  simultaneous  weakening  of 
the  physiological  activities  of  the  germ  occur- 
ring in  both  cases.  The  hereditary  repression 
of  such  an  important  morphological  character- 
istic as  spore-formation  was,  however,  not 
effected. 

A  mode  of  spore-formation  similar  to  that 
of  bacteria  has  as  yet  been  observed  only 
among  some  monads  and  flagellates — as  in 
the  so-called  cyst-formation,  for  example,  in 

1  Ann.  de  1'Inst.  Pasteur,  1890,  p.  24. 

2  Le  Bull,  med.,  1892,  No.  35;  La  Semaine  m<*d.,  1892,  No.  40. 

3 


34  BACTERIOLOGY. 

Monas    (Spumelld)    vulgaris    and    in     Chro- 
muhna. 

Aided  by  the  foregoing  facts,  we  may  attempt 
to  advance  beyond  Conn's  "  form-genera  "  and 
"  form-species  "  of  bacteria  to  a  conception  of 
natural  genera  and  species.  According  to 
Hueppe  and  De  Bary,  the  endosporous  bacteria 
must  be  fundamentally  separated  from  the  ar- 
throsporous.  For  the  sake  of  clearness,  let  us 
cite  some  examples.  The  specific  disease 
germs  found  in  anthrax,  typhoid  fever,  diph- 
theria and  tuberculosis  have  the  form  of  rods 
and  are  consequently  known  in  medical  liter- 
ature as  Bacilli.  But  the  anthrax  rods,  in 
the  light  of  their  whole  life  history,  belong  to 
a  species  that  forms  filaments  and  produces 
endospores  of  a  well-known  and  characteristic 
kind ;  the  bacteria  of  typhoid  fever  and  of 
diphtheria  form  no  endospores,  and  the  tubercle 
rods  probably  form  chlamydospores.  Accord- 
ing to  Cohn's  earlier  view  the  genera  Bacillus 
and  Bacterium  were  to  be  distinguished  only 
by  the  length  of  the  rods,  but  according  to  his 
later  conception  the  difference  lies  not  in  the 
dimensions  of  the  rods,  but  in  the  fact  that 
the  one  forms  endospores  while  the  other  does 
not.  In  accord  with  this  terminology,  there- 
fore, the  anthrax  rods  belong  to  the  genus 
Bacillus,  the  typhoid  and  diphtheria  rods  to 


THE   STRUCTURE    OF   BACTERIA.  35 

the  genus  Bacterium  or  Arthrobacterium,  and 
the  tubercle  rods  are  not  true  bacteria  at  all, 
but  a  parasitic  form  of  the  tubercle  mould. 

A  step  further  indeed  may  now  be  taken. 
The  name  Bacillus  may  be  limited  to  that 
genus  in  which  the  rods  undergo  no  change  in 
shape  during  spore-formation,  and  we  may  use 
the  term  Clostridium  for  that  genus  in  which 
the  rods  are  spindle-shaped  or  become  spindle- 
shaped  during  spore-formation,  and  designate 
as  Plectridium  that  in  which  the  cells  are 
shaped  like  a  drumstick  or  become  so  shaped 
through  the  development  of  endospores.  With 
reference  to  spore-formation,  therefore,  there 
are  among  the  rod  bacteria  three  genera  of 
endosporous  and  one  of  arthrosporous  bacteria. 
These  may  be  still  further  analyzed  into  sub- 
genera  if  we  take  into  consideration  the  form 
of  the  spores,  or,  as  Fischer  has  suggested,  the 
character  of  the  flagella. 

Among  the  spiral  bacteria  Cohn  constituted 
the  form-genera  Vibrio,  Spirochczte  and  Spi- 
rillum merely  upon  the  basis  of  the  form 
of  spiral.  I  would  establish  here  a  division 
into  natural  genera,  calling  those  spirals 
which  do  not  change  in  shape  during  endo- 
spore-formation  Spirillum,  and  applying  the 
name  Vibrio  to  those  that  become  swollen  in 
some  one  place  when  endospores  are  formed, 


36 


1      2      3 


B 

*<? 


*   0*» 

34567 


Fig.  19.  Cholera  asiatica. 

A.  Comma  bacilli,  1-4  after  drawings  ;  4,  twisted  coil,  so-called 
Spirodiscus,   (about   I  :  1200)  ;  5,  6,  spiral  filaments  with  spir- 
ulina  twistings  (after  photographs,  about  I  :  700). 

B.  Ripe  arthrospores  (after  photographs),  about  I  :  1000. 

C.  i  and  2,  Arthrospores  in  filaments  (after  van  Ermenghem, 
from  photograph),  about  i  :  700. 

3-7,  germinating  arthrospores  (after  photographs  by  Pertik, 
I  :  1200). 

and  Spirochcete  to  those  that  form  arthrospores 
(Fig.  19).  Under  this  nomenclature,  the 
specific  germ  of  Asiatic  cholera  would  be  de- 
signated as  Spirochcete,  although  in  medical 
literature  the  three  names,  Vibrio,  Spiroch&te 
and  Spirillum  are  used  interchangeably  and 
quite  arbitrarily.  The  older  usage  has  no  harm- 
ful effect  if  only  there  is  a  clear  understanding 


OX 


THE   STRUCTURE   OF   BACTERIA.  37 

of  what  is  really  meant,  but  it  has  had  a  soine= 
what  cramping  influence  upon  the  develop- 
ment of  bacteriological  nomenclature,  and  its 
disadvantages  may  still  be  frequently  perceived. 
The  statements  thus  far  made  might  well 
lead  to  the  conjecture  that  the  genera  hitherto 
established  fall  short  of  expressing  all  the 
known  facts.  It  is  clear,  in  fact,  that  all  the 
essays  at  classification  made  by  F.  Cohn, 
J.  Schroter,  Zopf,  De  Bary,  Hueppe,  Migula 
and  A.  Fischer  have  their  defects ;  but  botan- 
ists are  almost  unanimous  in  accepting  the 
essential  features  of  the  position  taken  by 
Cohn,  De  Bary  and  Hueppe.  Much  would  be 
gained,  therefore,  if  those  physicians  and 
technical  workers  who  have  to  do  with  bacteri- 
ology would  keep  in  mind  the  following  table 
of  orientation  which  at  least  excludes  gross 
errors  : 

I.  Coccacea,  producing  in  the  vegetative  state  coccus 
forms. 

1.  Micrococcus,  characterized  by  irregular  disposi- 
tion   of  the  cells  and  cell-groups ;  endospores 
as  yet  unknown  (Fig  8). 

2.  Sarcina,  forming  tetrads  and  balelike  packets  of 
cells  ;  endospores  unquestionably  observed  (Fig. 

7). 

3.  Streptococcus,  forming  spores ;  arthrospores  un- 
questionably   observed,     endospores     doubtful 
(Fig.  4). 


38  BACTERIOLOGY. 

II.  Barter iacece,  producing  in   the  vegetative  condition 
rod-forms  which  are  grouped  in  chains  or  filaments. 

1.  Arthrobacterium,  forming  arthrospores,  or  Bac- 
terium, forming  no  endospores  (Fig.  3). 

2.  Bacillus ;  with   endospore   formation  (Fig.  18). 
Sub-genera^.  Bacillus;  straight  rods. 

b.  Clostridium  ;  spindle-shaped  rods. 

c.  Plectridium  ;  drumstick-shaped  rods. 

III.  Spirobacteriacece,   in  vegetative  condition  forming 
short  curved  rods  (comma-shaped,    S-shaped)   which 
may  elongate  into  spiral  filaments. 

1.  Spirochcete,  without  endospores  and  with  arthro- 
spores (Fig.  19). 

2.  Vibrio,  with   endospores ;  the    cell  changes   in 
shape  during  spore-formation. 

3.  Spirillum,  with  endospores ;  the  cell  does  not 
change  its  form. 

IV.  Leptothrichecz,  forming  in  the  vegetative  stage  rods 
which  unite  in  filaments. 

1.  Leptothrix  is  distinguished  from  the  filamentous 
chains  of  arthrosporous  bacteria  by  the  fact  that 
the  filaments  are   differentiated  into   base   and 
apex. 

2.  Beggiatoa,  filaments   without  sheath  ;  the   cells 
contain  sulphur  granules  (Fig.  i,  i  and 5). 

3.  Phragmidiothrix ;    the    threads    are  segmented 
into  shallow  disks    which    may    fall    apart  into 
half-disks,  quadrants  and  finally  spheres. 

4.  Crenothrix ;  the   thread  possesses   a  sheath   in 
which  there  is  usually  a  deposit   of   iron    (Fig. 

13). 

V.  Cladothrichea ;   the  vegetative   cells  belong  to   the 
rod-forms,  the  rods  have  a  sheath  and  show   branch- 
ing. 

Cladothrix  (Figs.  5  and  21). 


1. 


2. 


t, 


Fig.  18. — Anthrax  bacteria. 

1.  From  spleen  pulp,  (i:  1200). 

2.  From  the  blood,  showing  possession  of  capsule,  (1:1000). 

3.  Edge  of  a  culture  showing  filamentous  windings  of  the 
so-called  spirulina  type,  (1:300). 

4.  Spore  formation,  (1:500). 


THE   STRUCTURE   OF   BACTERIA.  39 

Assuming  that  life  originated  upon  our 
planet,  the  first  living  things  must  have  been 
so  organized  that  their  metabolic  processes 
were  more  like  those  of  plants  than  of  animals  ; 
in  a  word,  the  primitive  organisms  must  have 
been  holophytic,  since  to  holophytes  alone  are 
saprophytes  able  to  attach  themselves.  It  is 
therefore  suggestive  that,  besides  physiological 
correspondences  to  be  noted  later,  the  structure 
of  the  gonidia-forming  or  arthrosporous  bacteria 
shows  a  progressive  differentiation  or  evolution 
from  the  simplest  bacterial  forms  and  species 
through  to  the  Cyanophycece,  a  group  of  blue- 
green  algae  which  may  be  regarded  as  an  unde- 
veloped branch  of  the  plant  kingdom.  On  the 
other  hand,  the  formation  of  endospores  and  the 
possession  of  flagella  are  facts  that  indicate 
phylogenetic  relations  with  the  monads  or  flag- 
ellates, a  group  usually  reckoned  as  animals. 
Physiologically  also  a  double  affinity  is  mani- 
fested, since  bacteria  display  almost  the  same 
capacity  for  building  up  organic  substance  as 
for  breaking  it  down. 

It  was  remarked  by  Cohn  that  a  complete 
parallelism  existed  between  the  genera  now 
regarded  as  arthrosporous  bacteria  and  certain 
groups  of  the  fission-algae  (Spaltalgen}.  Cohn, 
indeed,  already  departing  from  his  purely 
morphological  standpoint,  established  two 


40  BACTERIOLOGY. 

groups  of  distinct  phylogenetic  value  when  he 
placed  zooglcea-forming  bacteria  along  with 
zooglcea-forming  schizophytes  in  one  group, 
and  filament-forming  bacteria  with  filament 
forming  algae  in  a  second  and  related  group. 
These  distinguishing  marks,  howrever,  as  Zopf 
proved  later,  were  not  natural  ones,  and  the 
stronger  emphasis  subsequently  laid  upon 
fructification  yielded  the  first  hint  of  the  above- 
mentioned  affinities.  But  Cohn,  understand- 
ing the  close  phylogenetic  relations,  was  right 
in  some  details  and  correctly  ranked  Leu- 
conostoc  with  the  bacteria,  Nosloc  with  the 
Schizophytes,  Beggiatoa  with  Oscillaria,  Cre- 
nothrix  with  Chamczsiphon  and  Cladothrix 
with  Tolypothrix.  Botanists  and  zoologists 
have  in  general  assented  to  the  view  taken  by 
Cohn,  Hueppe  and  De  Bary  according  to  which 
two  groups  phylogenetically  distinct  are  united 
under  the  name  of  bacteria. 

Several  years  ago  Brefeld  asserted  that  those 
organisms  passing  under  the  name  of  yeasts, 
budding-fungi  or  Saccharomyces  did  not  form 
a  true  natural  group  but  were  specialized  forms 
of  various  species  of  moulds.  Hansen  main- 
tained, in  opposition  to  this,  that  the  species 
of  Saccharomyces  that  formed  endospores  were 
to  be  regarded  as  an  independent  natural 


THE  STRUCTURE  OF  BACTERIA.       41 

group.  Lately  Juhler x  claims  to  have  dis- 
covered that  the  mould  concerned  in  the  sake 
fermentation  develops  bud-like  forms  which 
produce  endospores,  and  A.  Jorgensen  2  main- 
tains that  one  of  the  wine-yeasts,  a  true  endo- 
spore-forming  variety,  is  merely  a  stage  in 
the  life-cycle  of  a  mould,  which,  upon  alkaline 
media,  grows  in  the  semblance  of  the  mould 
Chalara,  and  upon  acid  media  in  that  of  De- 
matium.  In  similar  fashion  L.  Klein  looked 
upon  the  arthrosporous  bacteria  as  degenerate 
Schizophytes,  as  Cyanophycetz  indeed,  which 
had  lost  their  chlorophyl  and  become  sapro- 
phytic.  It  is  true  he  abandoned  this  view  after 
Hueppe  had  demonstrated  the  ability  of  color- 
less microbes  to  assimilate  carbon  dioxide  and 
thus  to  exist  like  true  plants,  a  point  to  which 
I  shall  return  presently. 

There  are  cogent  reasons  for  accepting  the 
opinion  that  still  a  third  group  of  quite  differ- 
ent phylogenetic  value  should  be  recognized 
among  the  organisms  hitherto  classed  as  bac- 
teria. In  cultures  of  the  ray-fungus  true 
coccus  and  rod-forms  occur  which  appear  like 
undoubted  bacteria.  Since,  however,  the 
method  of  branching  of  the  filaments  is  not 

1  Centralbl.  f.  Bakt.  Abth.  II.,  I.,  1895,  p.  16,  p.  326. 

2  Centralbl.  f.  Bakt.  Abth.  II.,  I.,  1895,  p.  321.     See   also  Klocker 
and  Schioning,  Annal.  de  Microg.,  IX.,  1897,  Nos.  6-8. 


42  BACTERIOLOGY. 

like  that  of  Cladothrix,  the  Actimomyces  fun- 
gus must  after  all  be  regarded  as  a  mould. 
Till  recently  the  tubercle  bacillus  was  re- 
garded as  an  especially  typical  bacterium,  and 
when  stained  differentially,  the  shining  red 
band  stood  out  in  fine  contrast  with  the  blue 
background,  a  most  beautiful  example  of  a 
bacillus.  But  Roux,  Nocard  and  Metschni- 
koff,  as  well  as  more  recently  E.  Klein  and 
Maffucci,  observed  that  the  tubercle  bacilli  ob- 
tained from  cases  of  fowl  tuberculosis  exhibit 
a  sort  of  branching  ;  and  Metschnikoff ,  laying 
emphasis  upon  the  filament-forming  character 
of  the  organism,  placed  it  with  the  Lepto- 
thrichece  or  Cladothriche<z  and  called  it  Sclero- 
thrix.  For  some  time  evidence  has  been 
accumulating  that  the  opinion  of  Koch,  who 
had  regarded  the  organism  as  forming  endo- 
spores  and  had  hence  correctly  conferred 
upon  it  the  name  of  tubercle  bacillus,  and  his 
corresponding  schematic  figure  were  errone- 
ous. Upon  the  basis  of  further  investigations 
which  revealed  branching  even  in  the  microbe 
of  mammalian  tuberculosis, — investigations 
supplemented  by  my  pupil  Fischel, — I  have 
arrived  at  the  definite  opinion  that  the  tubercle 
bacillus  is  the  parasitic  growth-form  of  a  pleo- 
morphic  mould  and  is  not  a  true  bacterium  at 
all,  but,  in  respect  to  its  morphology,  is  closely 


P'ig.  20. — The  Germ  of  Tuberculosis. 

a,  ordinary  forms  found  in  cultures  and  sputum  (after  pho- 
tographs), about  i :  900. 

b,  Shows  plasmolyzed  cell  contents,  so-called  coccothrix 
'   forms,  (i :  1250). 

<r,  portion  of  the  edge  of  a  fresh  culture  of  the  germ  of 
mammalian  tuberculosis,  unstained,  (about  1:2000). 

d,  stained, i-3,after  photographs  by  F.Fischel,  i,the  germof 
avian  tuberculosis  from  glycerin  agar,  2,  3,  the  germ  of  mam- 
malian tuberculosis  from  egg  cultures;  4,  mammalian  cultures 
from  glycerin  agar,  Hayo  Bruns.  (1-3,  about  i:  1200;  4,  i:  1000) 
<?,  g,  h,  Formation  of  Chlamydospores;  ^,  mammalian  tuber- 
culosis (after  photographs,  r  •  9000);  g,  from  sputum  (drawing 
after  Coppen  Jones,  i:  1250);  ^.chlamydosporesof  Mucorfor 
comparison;  ft  branching  of  filaments  'after  Coppen  Jones), 
i :  1250;  at  x  it  can  be  seen  that  the  vacuoles  extend  from  the 
main  stem  into  the  side  branches,  as  in  k,  a  hypha  of  Peni- 
cillium,  thus  showing  the  existence  of  "true"  branching. 


THE   STRUCTURE    OF   BACTERIA.  43 

related  to  the  ray-fungus.  Coppen  Jones  has 
subsequently  confirmed  these  results,  and  has 
made  it  appear  likely  that  this  mould  possesses 
a  kind  of  fructification  resembling  chlamydo- 
spore-formation.  Its  mode  of  branching  also 
speaks  for  its  mould  nature  (Fig.  20).  In 
spite  of  these  facts,  physicians  have  continued 
to  call  this  organism  the  tubercle  bacillus. 
This  would  be  a  matter  of  indifference  if  it 
were  not  for  the  unavoidable  confusion  brought 
about  by  the  persistence  likewise  of  Koch's 
totally  inaccurate  figure.  But  a  gradual 
change  of  opinion  seems  to  be  coming  about, 
and  very  recently  Hayo  Bruns  '  and  Semmer 2 
have  confirmed  the  pleomorphism  of  the  tuber- 
cle bacillus.3 

Occasionally  branching  is  observed,  too, 
among  organisms  which  are  presumably  true 
bacteria,  as  Metschnikoff  has  discovered  in  the 
case  of  the  comma-bacilli  of  Asiatic  cholera,  C. 
Frankel  in  the  so-called  diphtheria  bacilli  and 
Semmer  in  the  bacteria  of  glanders  which,  as 
arthrosporous  species,  do  not  belong  at  all  to 
the  bacilli.  Eijkman4  has  found  branched 
bacteria  in  the  molasses  fermentation  of  rice 
(Fig.  22).  Up  to  the  present  it  has  not  been 

1  Centralbl.  f.  Bakt.  XVII.,  1895,  P-  8l7- 

2  Deutsche  Zeitschr.    f.  Tiermedizin,  XXI.,  p.  212. 

8  See  also  Marpmann,  Centralbl.  f.  Bakt.  XXII.,  1897,  p.  582. 
4  Centralbl.  f.  Bakt.,  XVI.,  p.  97. 


44 


BACTERIOLOGY. 


Fig.  2i.—Cladothrix  dichotoma. 

False  branching  ;  the  original  direction  of  growth  corresponds 
to  the  line,  r,  a,  p  ;  by  the  pushing  of  cells  to  one  side  and  their 
subsequent  growth  the  branches,  n,  n,  arise  ;  at  the  apex  of  these 
the  structure  is  plainly  seen  to  be  that  of  a  chain  of  cylindrical 
cells.  The  false  branching  is  a  special  form  of  branching,  b, 
a  piece  of  a  filament  with  distinct  segmentation  ;  in  the  upper 

gart,  the  sheath  is  nearly  emptied  of  cells.     (Drawing  after  De 
ary)  I  :  600. 

determined  whether  the  branching  is  of  the 
same  type  as  the  pseudo-branching  of  the  Cla- 
dothrichece,  i.e.,  of  the  pleoinorphic  arthrospo- 


THE    STRUCTURE    OF   BACTERIA. 


45 


es  fermentation  occurring 
in  the  manufacture  of  ar- 
rack in  Batavia  (after  Vor- 
dermann  and  Eijkman). 


rous  bacteria,  or  is  like  the  true  branching 
of  moulds.  Schottelius  x  observed  on  certain 
occasions  a  cell  division 
so  irregular  in  character 
in  the  "  miracle  bac- 
teria" as  at  once  to 
suggest  budding  of  a 
torula  or  saccharomyces 

nature,  and  Wood  found  Fig  22  J^acinU3  fr0m  moiass- 
a  torula-form  among 
anthrax  bacilli  that  were 
shut  out  from  free  access 
of  air,  without  however  being  able  to  initiate  de- 
velopment with  it.  Finally  Koch  and  Hosaeus 2 
have  discovered  a  kind  of  bacterium  with  a 
gelatinous  stalk  which  reminds  one  of  a  diatom 
(Fig.  23).  The  fore- 
going facts  clearly  dem- 
onstrate that  the  usual 
designations  "  bacteria" 
and  "  bacteriology  "  are 
not  adequate  to  repre- 
sent correctly  and  scien- 
tifically the  actual  sitU-  Fig.  23.— B.  pediculatum  from 

"  frog-spawn"  of  sugar  man- 

atlOIl.  ufactories  (after  A.  Koch  and 

f-^^  1 .  j          H.  Hosaeus). 

The         complicated 
structure    which    Ehrenberg   claimed  was  to 

1  Festschr.  f.  A.v.  Kolliker,  Leipzig,  1887. 

2  Centralbl.  f.  Bakt.  XVI.,  1897,  p.  225. 


46  BACTERIOLOGY. 

be  found  in  bacteria  and  the  "  infusion  ani- 
mals "  ought,  in  my  opinion,  to  have  weighed 
against  the  doctrine  of  "  spontaneous  gener- 
ation." We  are  now  no  longer  able  to  accept 
Ehrenberg's  conception  of  the  structure  of  bac- 
teria, yet  the  knowledge  we  do  possess  is 
sufficient  to  discredit  the  notion  that  bacteria 
can  arise  by  spontaneous  generation.  The 
bacterial  cell  is  much  too  complicated  and 
too  far  removed  from  the  ideal  "  simplest 
cell "  to  admit  of  this  view.  The  experi- 
ments devised  to  support  the  belief  in  their 
spontaneous  development  out  of  inorganic 
or  altogether  lifeless  material  have  moreover 
always  miscarried.  The  one  undeniable  fact 
in  the  matter  is  that  certain  granular  proto- 
plasmic elements  can  outlast  the  life  of  the  cell. 
In  this  latter  category  belong  especially 
those  effects  due  to  the  so-called  lifeless  fer- 
ments or  enzymes.  The  digestive  ferments 
of  the  higher  animals  are  in  the  first  instance 
nothing  but  extruded  cell-protoplasm  and  often 
appear  like  a  sort  of  cell-slime.  Among  bac- 
teria also  such  ferments  occur  independently 
of  the  life  of  the  cell.  Fermentative  manifesta- 
tions, however,  constitute  only  a  limited  part 
of  the  vital  phenomena  of  the  cell.  The 
formation  of  enzymes,  outlasting  the  cell  and 
indeed  to  a  certain  degree  independent  of  it,  is 


THE   STRUCTURE   OF   BACTERIA.  47 

always  dependent  npon  the  integrity  of  the 
living  cell  which  alone  is  able  to  pass  on  the 
torch  of  life  in  legitimate  succession. 

Statements  about  the  origin  of  bacteria 
from  other  cells  and  cell  elements  through 
"  anamorphosis  of  protoplasm  " — really  a  sort 
of  modified  spontaneous  generation — rest  upon 
an  error  due  to  the  mistaking  for  bacteria  of 
cell-granules  in  milk,  blood  and  tissues,  as  well 
as  of  fibrin  secretions  and  artificially  altered 
nuclear  elements.  Fibrin  threads  have  also 
been  mistaken  for  the  mycelia  of  moulds. 
Fokker  described  the  origin  of  the  anthrax 
bacilli  as  taking  place  by  "  heterogenesis  "  out 
of  other  cells,  but  Koch  proved  that  elongated 
cell-nuclei  had  been  mistaken  for  bacteria. 
Roy,  Brown  .and  Sherrington  discovered  fila- 
ments in  the  wall  of  the  intestine  which  they 
identified  as  hyphaeof  one  of  the  Chytridiacea 
and  believed  to  be  the  cause  of  cholera  till 
H.  Kiihne  and  Hueppe  showed  that  the  fila- 
ments were  not  mould-hyphae  at  all,  but  shreds 
of  fibrin.  In  like  manner  Lacerda  believed 
that  he  had  discovered  the  essential  element 
of  snake-venom  to  be  micrococci,  but  Hueppe 
was  able  to  prove  that  these  supposititious  mi- 
crococci were  granules  derived  from  the  gland- 
cells. 

The  ferments,  by  virtue  of  their  independ- 


48  BACTERIOLOGY. 

ence  of  the  cells  producing  them  are,  so  to 
speak,  "  active  "  proteid,  a  kind  of  intermed- 
iate stage  between  lifeless  "  nutritional  "  pro- 
teid and  living  cells.  Active  proteid  possesses 
another  property  which  has  become  recognized 
through  the  medium  of  bacteriological  inves- 
tigation, that,  namely,  of  killing  bacteria  and 
influencing  the  activity  of  bacterial  poisons. 
This  property  of  "  activity "  is  acquired  by 
virtue  of  the  vitality  of  the  cell,  but  is  to 
some  extent  independent;  it  can  outlast  the 
mother  cell  and  may  be  preserved  for  some 
time  by  the  addition  of  chloroform,  carbolic 
acid,  cresol,  or  toluene,  or  by  careful  drying, 
while  heat,  light  and  putrefaction  destroy  it. 
It  is  a  fact  of  interest  in  this  connection  that, 
according  to  Scholl,  such  an  "  activity  "  which 
has  been  removed  by  heat  can  be  partly  re- 
stored by  purely  chemical  measures  and  thus 
the  distinction  between  lifeless  and  living, 
active  and  passive  proteid  still  further  obliter- 
ated. 

After  all  is  said,  spontaneous  generation  re- 
mains up  to  the  present  time  only  an  unavoid- 
able general  hypothesis.  The  attempts  of 
Liebig,  Thomson,  and  Helmholtz  to  refer  the 
origin  of  life  on  our  planet  to  importation  from 
other  heavenly  bodies  evades  the  question  and 
leaves  it  as  obscure  as  before.  In  the  synthesis 


THE   STRUCTURE   OF   BACTERIA.  49 

of  proteid  substances,  we  approach  the  question 
as  we  have  just  seen,  from  another  side  and 
here  also  bacteriological  researches  have  been 
of  fundamental  importance.  Indirectly  these 
results  perhaps  support  the  theoretical  postu- 
late of  spontaneous  generation  since  they  seem 
to  efface  still  further  the  boundaries  between 
animal  and  plant,  the  organic  and  the  in- 
organic. 

4 


CHAPTER  II. 

THE  VITAL  PHENOMENA  OF  BACTERIA. 

IF  we  accept  the  nebular  hypothesis  of  the 
origin  of  the  solar  system,  we  must  believe 
that  the  first  living  things  developed  under 
conditions  which,  in  respect  to  temperature, 
light  and  atmospheric  oxygen,  departed  widely 
from  those  prevailing  at  the  present  time. 
The  atmosphere  must  have  been  poorer  in 
oxygen,  poorer  in  light  and  possessed  of  a 
higher  temperature.  In  view  of  this  fact,  it  is 
interesting  to  note  that  among  bacteria,  spe- 
cies are  found  that  are  able  to  live  without  free 
oxygen,  without  light,  and  at  a  relatively  high 
temperature  and  this  to  an  extent  known 
among  no  other  group  of  living  things. 

Anaerobiosis — Relations  to  Energy. 

To  the  genius  of  Pasteur  we  are  indebted 
for  the  remarkable  observation  that  microbes  or 
micro-organisms  can  live  without  free  oxygen. 
In  life  without  air — that  is  to  say,  without  the 
oxygen  of  the  air — in  the  absence  of  this  "  food 


THE   VITAL   PHENOMENA   OF   BACTERIA.          51 

of  life,"  oxygen  is  taken  from  chemical  com- 
pounds which,  in  consequence,  suffer  disinte- 
gration and  rearrangement  of  their  parts. 
Pasteur  observed  this  phenomenon  of  anaero- 
biosis  first  in  fermentations,  thereby  renewing 
acquaintance  with  a  process  previously  known 
to  some  alchemists,  and  described  as  a  "  fer- 
mentatio  clausal  It  is  really  a  question  of 
the  decomposition  of  very  unstable  bodies,  a 
process  resulting  from  the  disturbing  influ- 
ence of  molecular  movements  imparted  to 
these  bodies  by  the  substances  exciting  fer- 
mentation. 

In  the  chemical  building-up  of  the  body- 
substance  of  living  things  we  can  distinguish 
several  groups  of  phenomena  :  polymerization, 
a  sort  of  doubling  up  of  a  simpler  compound  ; 
synthesis,  a  union  of  different  kinds  of  simple 
compounds  into  one  more  complex  substance  ; 
formation  of  anhydride,  by  which  new  sub- 
stances arise  from  a  compound  through  the 
loss  of  water ;  and  reduction  or  loss  of  oxygen, 
which  is  brought  about  especially  by  the 
entrance  of  hydrogen  into  the  molecule.  The 
breaking  down  of  organic  bodies  in  and  through 
the  action  of  living  things  takes  place  through 
the  loosening  of  the  bonds  of  polymeriza- 
tion ;  through  hydration  or  entrance  of  water 
into  the  molecule ;  and  through  oxidation. 


52 


BACTERIOLOGY. 


The  following  examples  will  make  these  pro- 
cesses clear.  I  shall  at  first  use  intention- 
ally the  empirical  formulae,  taking  no  heed 
of  the  so-called  chemical  constitution  of  the 
compound,  and  leaving  unconsidered  the  dis- 
placement of  atoms  and  atomic  groups. 

Hydration  and  formation  of  anhydride  : 


3C6H1005    +    H20   =   CjgHggOn 
starch,  water,  maltose, 

C6H1005    +    H20   ==   C6H1206 
dextrin,          water,     grape-sugar. 

C12H22011    +    H20   ==   C6H1206 
cane-sugar,  water,     grape-sugar, 

or,  milk-sugar,  "     . 

Conversely  : 


C6H1005 
dextrine. 


C6H1206 
fruit-sugar. 
galactose. 


C6H12O6    —   H2O   =   C6H10O5 
grape-sugar,      water,          starch. 

Polymerization  and  breaking  up  of  polymers 


6CH2O      =      C6H12O6 
formaldehyde,       grape-sugar. 


Conversely : 


CCH180G    =    2C3H603 


sugar, 


lactic  acid. 


Decompositions  and  syntheses  : 


C6H18O6   =   2C2HCO 
sugar,  alcohol, 


2CO2 

carbonic  acid. 
(carbon  dioxide). 


or. 


C6H12O6     =     C4H8O8       +  .       2092         +          2H8 
sugar,  butyric  acid,    carbonic  acid,     hydrogen. 


THE   VITAL   PHENOMENA   OF   BACTERIA.          53 


Conversely  : 


C2H5N02     +     C7H602    ==  C9H9N03     +    H3O 
glycocoll,  benzole  acid,    hippuric  acid,     water, 
amido-acetic  acid, 
or  gelatin -sugar. 

Decompositions  and  syntheses,  with  simple  dis- 
placement or  shifting  of  atoms  : 

HCNO      +      NH3     =      NH4CNO  CON8H4 

cyanic  acid,     ammonia,    ammonium  cyanate,        urea. 

Conversely  : 

CON2H4  +  2H20   =   C03(NH4)2 

urea,          water,    ammonium  carbonate, 
-  2NH3        +        CO2          -K         H8O 
ammonia,        carbonic  acid,          water. 

Reductions  and  oxidations  : 

H2C03      =      CH20        +        08 
carbonic  acid,    formaldehyde,      oxygen. 

Reductions,  with  entrance  of  hydrogen  into  the 
molecule  : 

CH202      +      H2      =        CH20          +          H20 
formic  acid,     hydrogen,    formaldehyde,  water. 

Conversely : 

C2H60      +      02      =      C2H402     +    H20 
alcohol,          oxygen,        acetic  acid,      water, 
or,  C2H4O2     +     2O2      =        2CO2          +          2H2O 
acetic  acid,        oxygen,      carbonic  acid,  water. 

In  the  absence  of  oxygen  no  oxidation  can 
occur,  hence  a  smaller  quantity  of  energy  is 
liberated.  If,  for  example,  1,000  grams  of 
grape-sugar  be  burned  or  oxidized  to  carbonic 


54  BACTERIOLOGY. 

acid  and  water,  it  affords  3,939  heat-units  or 
calories  ;  if,  however,  it  be  split  into  butyric 
acid,  hydrogen  and  carbon  dioxide,  it  yields 
only  414  calories.  One  thousand  grams  of 
sugar  suffices  to  produce  3,939  calories  by 
means  of  complete  combustion  with  oxygen, 
while  by  means  of  the  above-mentioned  decom- 
position without  oxygen  9,514.5  grams  are 
necessary  to  the  production  of  the  same  num- 
ber. The  access  of  pure  atmospheric  oxygen 
consequently  makes  life  easy,  but  is  not  in- 
dispensable. The  energy  needed  for  the  pro- 
cesses of  life  can  be  procured  by  simple  decom- 
position, by  hydration  or  by  loosening  of  poly- 
merizations ;  in  none  of  these  chemical  actions 
is  access  of  free  oxygen  necessary,  and  all 
molecular  shif tings  may  take-  place  simply 
with  the  help  of  chemically  bound  oxygen.  If 
we  consider  anaerobiosis  from  the  point  of  view 
of  physics,  then,  it  is  seen  at  once  that  life  is 
carried  on  in  accordance  with  the  general  laws 
of  energy  and  that  there  can  be  no  especial  vital 
force.  The  maintenance  of  life  without  free 
oxygen  depends  solely  upon  the  presence  or 
absence  of  available  substances  which  can  be 
broken  up  with  sufficient  ease.  The  standard 
of  availability,  however,  is  very  different  for  dif- 
ferent microbes.  Pasteur  regarded  sugar,  Nae- 
geli  peptone,  and  Hueppe  true  proteid  substance 


THE   VITAL   PHENOMENA   OF  BACTERIA.         55 

as  suitable  pabulum.  I  have  also  succeeded  in 
finding  available  inorganic  sources  of  oxygen, 
thereby  somewhat  complicating  the  problem. 
Life  processes  carried  on  without  oxygen  do  not 
effect  any  profound  changes  in  the  organic  ma- 
terial which  is  broken  up,  but,  in  order  that 
the  living  organism  may  obtain  the  requisite 
quantity  of  energy  from  this  mode  of  life,  a 
proportionally  large  amount  of  material  must 
be  superficially  disintegrated.  Therein  lies 
the  mechanical  or  dynamic  foundation  for 
the  fact  that  a  small  quantity  of  a  ferment  is 
able  to  cause  the  production  of  much  alcohol, 
butyric  acid  or  lactic  acid,  and  that  parasites 
which  have  invaded  the  living  body  can  gen- 
erate intensely  poisonous  substances  out  of  the 
body-proteids. 

In  the  presence  of  oxygen  the  decompo- 
sition products  that  are  formed  by  the  attack  of 
anaerobic  microbes  are  further  decomposed 
and  oxidized  by  the  aerobes ;  they  are  there- 
by rendered  inert  and  consequently  harmless. 
From  alcohol  is  produced  acetic  acid  and  after- 
wards carbon  dioxide  ;  proteid-like  poisons  are 
broken  up  and  oxidized  into  harmless  bodies. 

Some  microbes,  the  obligatory  anaerobes, 
have  adapted  themselves  to  the  exclusive  use 
of  those  compounds  from  which  oxygen  can  be 
obtained,  and  others,  the  obligatory  aerobes,  are 


56  BACTERIOLOGY. 

able  to  live  only  in  the  presence  of  free  oxygen. 
Between  these  extreme  types  lie  the  larger 
number  of  species,  which  can  live  as  well  with 
as  without  free  oxygen  according  to  the  nature 
of  food-material  present ;  these  are  designated 
as  facultative  anaerobes  or  facultative  aerobes. 
Aerobiosis  and  anaerobiosis  must  not  be 
considered  ontologically.  They  are  results 
simply  of  adaptation  to  the  energetical  pro- 
cesses of  nutrition.  Substances  poor  in  nutri- 
tional value  may,  in  the  presence  of  air,  yield 
more  energy  through  oxidation  than  the  rich- 
est substance  through  simple  splitting.  On 
the  other  hand,  a  material  capable  of  being 
split  up  easily  may  at  first,  in  spite  of  the 
access  of  oxygen,  remain  exempt  from  oxida- 
tion and  only  later  and  secondarily  come  to  be 
oxidized,  for  the  reason  that  the  quantity  of 
energy  yielded  by  simple  splitting  is  sufficient 
for  the  need  of  the  microbe.  As  a  matter 
of  fact,  it  is  possible  to  accustom  obligatory 
anaerobes  to  life  in  the  air  and  air-living 
bacteria  to  anaerobiosis.  A  strict  anaerobe, 
Spirillum  rubrum,  which  came  into  my 
possession  and  which  produced  its  red  pig- 
ment only  in  the  absence  of  oxygen,  could  in 
a  short  time  be  cultivated  as  an  aerobe  ;  the 
same  measures  have  succeeded  with  the  Acti- 
nomyces  fungus,  and  Kitt  has  cultivated 


THE   VITAL   PHENOMENA   OF   BACTERIA.         57 

aerobically  the  obligatory  anaerobic  bacillus 
of  symptomatic  anthrax.  I  have  constrained, 
on  the  other  hand,  the  cholera  germ  to  adopt  an 
anaerobic  mode  of  life,  and  thereby  arrived  at 
an  explanation  of  its  growth  in  the  intestine 
and  the  intestinal  walls. 

It  might  be  possible,  in  an  extreme  case, 
to  bring  a  microbe,  ordinarily  causing  oxida- 
tion, to  such  a  point  that,  in  the  absence  of 
oxygen,  it  would  even  reduce  from  the  oxides 
the  selfsame  body,  the  power  to  oxidize  which 
was  its  first  known  peculiarity.  For  example, 
the  same  microbes  which,  in  the  presence  of 
oxygen,  oxidize  ammonia  to  nitric  acid  might, 
in  the  absence  of  oxygen,  reduce  the  nitric 
acid  to  ammonia.  I  have  on  hand  at  present 
some  unfinished  experiments  to  test  this  possi- 
bility. The  determining  cause  in  any  event 
lies  in  the  grouping  of  the  atoms  in  the  mole- 
cule which,  either  in  the  presence  of  oxygen 
or  in  its  absence,  is  torn  apart  by  the  disinte- 
grating impulse.  This  molecular  disintegra- 
tion is  not  necessarily  brought  about  only  by 
living  things ;  other  forms  of  motion  can  ac- 
complish the  same  result.  Duclaux  obtained 
by  insolation  a  sort  of  alcoholic  fermentation 
of  sugar,  and,  according  to  Ritsert,  light  and 
oxygen  together  effect  an  oxidation  of  fat. 

In  the  cultivation  of  anaerobes  upon  favor- 


58  BACTERIOLOGY. 

able  nutrient  material,  at  first,  in  spite  of  the 
presence  of  oxygen,  products  due  to  splitting 
are  formed,  and  it  is  only  subsequently  that 
oxidation  of  these  products  takes  place.  For 
this  reason,  it  is  necessary,  if  one  wishes  to  com- 
pel aerobes  to  grow  without  oxygen,  to  work 
with  them  in  a  young  condition.  Cholera  cul- 
tures are  virulent  when  young,  first  becoming 
impotent  through  access  of  air.  For  the  same 
reason  our  cultures  of  pathogenic  bacteria  upon 
gelatin,  agar,  and  potato,  and  in  broth,  are  gen- 
erally without  power  to  produce  disease,  since, 
in  consequence  of  the  restriction  of  metabolic 
activity  to  the  splitting  of  certain  substances, 
they  have  accustomed  themselves  so  thor- 
oughly to  a  metabolism  based  on  oxidation,  that 
the  poisons  that  wrere  formed  in  the  first  in- 
stance through  decomposition  are  rendered 
harmless  through  the  subsequent  oxidation. 
Ultimately,  therefore,  the  formation  of  these 
poisons  comes  to  a  standstill. 

Engelmann  I  actually  observed  that  one  spe- 
cies of  Spirillum  had  a  distinct  preference  for 
a  certain  tension  of  oxygen  and  always  took  up 
its  position  between  the  edge  and  centre  of  the 
drop  of  fluid  in  which  it  was  suspended,  at  a 
point  dependent  on  this  tension.  If  the  ten- 
sion of  the  oxygen  was  diminished  by  the 

i  Arch.  Neerland,  XXVIII,  p.  358. 


THE   VITAL    PHENOMENA   OF   BACTERIA.         59 

introduction  of  hydrogen,  the  bacterium  ap- 
proached the  edge  of  the  drop ;  if  the  tension 
was  raised  by  the  introduction  of  oxygen,  it 
drew  away  from  the  edge.  If  the  oxygen 
is  removed,  not  mechanically,  but  by  the  re- 
placement of  the  air  by  other  gases,  it  is  found 
that  carbon  dioxide  and  sulphuretted  hydro- 
gen are  poisons  for  bacteria,  while  hydrogen 
seems  to  have  no  effect  on  them.  In  the  fer- 
mentation industry  it  was  known  long  ago 
that  the  must  could  be  "  aerated  "  with  hy- 
drogen, and  that,  therefore,  not  the  addition 
of  oxygen,  but  the  removal  of  carbon  dioxide 
was  the  important  part  of  the  process. 

The  facts  of  anaerobiosis  are  of  great  im- 
portance to  technical  biology  and  to  pathology. 
Since,  under  strictly  anaerobiotic  conditions, 
any  secondary  oxidation  of  the  primary  decom- 
position products  is  impossible,  the  latter  accu- 
mulate without  formation  of  bye-products.  In 
the  technique  of  fermentation  this  fact  enters 
into  consideration  in  the  so-called  "  bottom  fer- 
mentation." In  disease,  the  possibility  of  ex- 
tracting physically  bound  oxygen  from  the  blood 
plasma  is  of  only  secondary  importance  ;  other- 
wise all  individuals  who  suffer  from  invasion  of 
the  blood  by  microscopic  organisms,  would  die 
from  carbonic  acid  poisoning.  Formation  of 
carbonic  acid,  however,  may,  as  a  symptom  of 


60  BACTERIOLOGY. 

oxidation,  contribute  to  increase  the  body  tem- 
perature, i.  e.,  to  produce  fever  (C.  Roser). 
Fever,  however,  is  generally  merely  the  ac- 
companiment of  a  disease,  the  more  impor- 
tant feature  being  the  formation  of  primary 
products  by  splitting  which  impart  to  individ- 
ual diseases  their  characteristics.  Braatz ' 
has  recently  laid  stress  on  the  fact  that  the 
microbes  in  suppurating  foci  are  living  with- 
out atmospheric  oxygen.  Hueppe 2  and  Scholl 3 
had  previously  shown  that,  in  cholera,  the 
comma  bacilli  produce  relatively  more  poison  in 
the  absence  of  air  than  in  its  presence,  and 
that  the  primary  anaerobic  poisons  formed  by 
decomposition  are  destroyed  upon  access  of  oxy- 
gen. With  anaerobic  cholera  cultures  I  suc- 
ceeded in  bringing  about  typical  diarrhoea  in 
animals  used  for  experiment ;  previously  this 
had  not  been  accomplished. 

Absence  of  air  has  a  further  effect ;  it 
enables  the  microbes  to  retain  for  a  long  time 
their  power  of  causing  fermentation,  of  pro- 
ducing poison  or  of  bringing  about  infection. 
Experiments  of  Fajans  and  Hueppe 4  have 
shown  that  cholera  cultures  retain  their  viru- 
lence for  weeks  and  even  months  under  anaero- 

1  Deutsche  med.  Wochensch.,  1890,  No.  46. 
'2  Deutsche  med.  Wochensch.,  1891,   No.  53. 
8Berl.  klin.  Wochensch.,  1890,  No.  11,  12. 
*  Arch.  f.  Hyg.,  XX. 


THE   VITAL   PHENOMENA   OF   BACTERIA.         6 1 

bic  conditions  after  parallel  cultures  which 
have  been  freely  exposed  to  air  have  long 
since  lost  their  potency.  Bunzl-Federn  has 
shown  the  same  thing  to  be  true  of  the  very 
delicate  pneumonia  germs. 

Light  and  Temperature.     Sterilization. 

Adaptation  to  light  is  developed  in  different 
degrees.  While  most  kinds  of  bacteria  thrive 
in  the  absence  of  light  others  become  as  it  were 
dormant,  and  when  these  latter  are  brought 
again  into  the  presence  of  light  an  increase  of 
movement  sometimes  occurs,  as  has  been  ob- 
served by  Engelmann.  One  species  indeed 
showed  this  sensitiveness  to  light  in  so  striking 
a  manner  that  it  was  named  by  this  observer 
Bacterium  photometricum.  On  the  other  hand 
many  bacteria  are  destroyed  by  direct  sun- 
light. The  existence  of  any  special  influence 
of  the  presence  of  bacterial  pigment  upon 
behavior  to  light  can  as  a  rule  not  be  demon- 
strated.1 In  one  species  containing  chlorophyl, 
Bacterium  chlorinum,  Engelmann  has  demon- 
strated the  giving  off  of  a  slight  quantity  of 
oxygen.  Zopf  has  found  also  that  cultures  of 
the  purple  bacteria  develop  more  luxuriantly 
on  that  side  of  an  aquarium  which  is  turned 
towards  the  light.  According  to  Engelmann, 

1  [See,  however,  Ewart,  Journ.  Linn.  Soc.  Bot.,  1897,  No.  228]. 


r UKIV 


62  BACTERIOLOGY. 

however,  this  purple  pigment  is  like  chlorophyl 
or  leaf -green,  and  must  be  regarded  as  a  feebly- 
acting  chromophyl  which  effects  possible  as- 
similation of  carbon  dioxide. 

A  specially  striking  adaptation  to  life  in  the 
presence  of  air  is  seen  in  the  phenomenon  of 
phosphorescence  or  luminosity.  This  phenom- 
enon, which  has  been  investigated  by  Pfliiger,1 
Fischer2  and  Beyerinck,3  is  to  be  noticed  in 
decomposing  meat  and  fish  and  particularly  in 
the  phosphorescence  of  sea-water.  As  has 
been  shown  by  Beyerinck  and  my  assistant 
Weleminsky,  it  is  a  vital  phenomenon  which 
passes  away  with  death.  During  life  it  is  de- 
pendent upon  an  abundant  supply  of  oxygen. 
If  the  oxygen  is  replaced  by  another  gas,  the 
luminosity  disappears,  only  to  appear  again 
when  oxygen  is  readmitted.  Those  luminous 
bacteria  which  are  facultative  anaerobes  do  not 
show  phosphorescence  in  the  anaerobiotic  con- 
dition, but  only  upon  the  entrance  of  oxygen. 
The  power  of  luminosity  may  be  lost  in 
cultures. 

The  remarkable  substances  known  as 
bacterial  pigments,  among  which  we  find  almost 
all  colors  represented,  belong  to  quite  diverse 

1  Pfluger's  Arch.  Bd.  X.,  1874,  and  Bd.  XL,  1875. 

2  Die  Bakterien  des  Meeres  nach  den  Untersuchungen  der  Plank- 
ton-Expedition, 1894. 

3  Arch.  Neerd.  XXIIL,  1889. 


THE    VITAL   PHENOMENA   OF   BACTERIA.         63 

chemical  groups.  Some  of  these  pigments  arise 
from  the  decomposition  of  proteid  bodies  and 
themselves  manifest,  in  part  at  least,  proteid 
characters.  Hoffa  and  Enoch  succeeded  in  ex- 
tracting from  fluorescing  cultures  a  proteid-like 
body  which  in  solution  gave  a  fine  green  fluor- 
escence. Other  pigments,  as  for  instance,  the 
familiar  red  pigment  with  green  fluorescence 
manufactured  by  the  "  miracle  germ  "  are  re- 
lated chemically  to  the  aniline  dyes.  Hueppe 
has  shown  that  the  magnificent  ultramarine 
blue  pigment  of  blue  milk  is  formed  out  of 
proteid  substance  and  also  out  of  ammonia  and 
a  substance  which  is  formed  both  analytically 
from  sugar  and  synthetically  from  milk-sugar. 
Zopf  and  Overbeck,1  finally,  have  ascertained 
that  some  bacterial  pigments  belongs  to  the 
lipochromes  or  fatty  pigments  ;  according  to 
Biitschli  perhaps  the  bacterio-purpurin  of  Beg- 
giatoa  also  belongs  here. 

Investigations  by  Forster 2  and  Fischer 3 
have  shown  that  bacteria  exist  in  the  ocean 
and  in  the  soil  which  can  multiply  at  o°  C. 
They  observed,  for  example,  that  M.  phos- 
phor escens  grew  upon  fish  and  evoked  visible 
luminosity  at  this  temperature  in  6—8  days. 
Zopf  observed  a  species  found  in  surface  water 

iNov.  Act  d.  Kais.    Leop.-Carol  Akad.  LV.,  1891,  No.  7. 

2  Centralbl.  f.  Bakt.  II.,  1887,  XII.,  1892. 

3  Centralbl.  f.  Bakt.  IV.,  1888. 


64  BACTERIOLOGY. 

which  formed  spores  even  when  the  water  was 
covered  with  ice.  The  majority  of  soil  and 
water  bacteria,  however,  pass  into  a  kind  of 
cold  rigor  when  the  temperature  falls  to  a  low 
point  and  are  no  longer  able  to  increase.  They 
grow  and  multiply  only  at  a  temperature  above 
5°  C,  and  thrive  best  at  about  20°  C. ;  the  path- 
ogenic germs  find  their  optimum  at  the  blood 
temperature  of  about  37°.  Globig,1  however, 
discovered  species  in  soil  which  have  adapted 
themselves  to  the  high  temperature  of  the 
upper  layers  of  the  soil,  a  temperature  which, 
through  direct  action  of  the  sun's  rays,  ranges 
between  15°  and  68°  ;  he  has  also  observed 
others  which  grow  only  between  54°  and  64°,  at 
a  temperature,  that  is,  at  which  proteid  is  usual- 
ly altered.  Van  Tieghem  observed  one  species 
which  grows  and  forms  spores  even  at  74°, 
and  refuses  to  multiply  only  when  77°  is 
reached.  Not  even  those  Cyanophycecz  and 
diatoms  which  grow  upon  the  deposits  in  hot 
springs  are  able  to  endure  as  high  a  tempera- 
ture. 

The  temperature  necessary  to  produce  death 
varies  also  extraordinarily.  Simple  freezing 
destroys  many  vegetative  cells,  but  man}^  on 
the  other  hand,  withstand  the  shock.  Ex- 
posure to  rapid  alternation  of  freezing  and 

1  Zeitschr.  f.  Hyg.,  III.,  1888.- 


THE   VITAL   PHENOMENA   OF   BACTERIA.         65 

thawing  is  more  injurious  than  a  long  exposure 
to  a  temperature  below  o°.  Spores  endure 
a  still  lower  temperature  than  the  vegetative 
forms  and,  indeed,  according  to  Pictet  and 
Young,  they  may  survive  for  20  hours  at  a 
temperature  of  -120°.  According  to  recent 
experiments  by  Pictet,1  they  survive  and  are 
able  to  multiply  after  being  embedded  for  a 
short  time  in  frozen  oxygen  at  -213°. 

Although,  according  to  Duclaux,  the  vege- 
tative cells  of  some  species  are  able  to  with- 
stand a  temperature  of  from  9O°-ioo°,  most 
species  enter  into  a  kind  of  heat  rigor  at  42°- 
45°  and  like  other  organisms  are  killed  by 
temperatures  of  over  55°.  The  spores  of  the 
more  resistant  species  are  destroyed  by  boiling 
water  and  steam  only  after  6  hours  exposure, 
and  by  steam  under  pressure,  at  no°-i2o°, 
after  half  an  hour.  (In  contrast  to  this,  the 
digestive  and  bacterial  enzymes  when  in  the 
moist  condition  are  destroyed  by  temperatures 
of  above  70°  and  of  about -i  00°.  In  the  dry 
condition,  however,  these  enzymes  withstand 
the  action  of  high  temperatures  up  to  -170°.) 
The  dense  membrane  of  the  endospores  and  the 
relatively  small  amount  of  water  contained  in 
their  protoplasm  protects  them  effectively 
against  temperature  oscillations. 

1  Arch,  des  sci.  phys  et  nat.  XXX.,  1893,  P-  293- 


66  BACTERIOLOGY. 

Some  further  effects  of  temperature  are 
worthy  of  note.  Pasteur  discovered  that  if 
anthrax  bacilli  are  cultivated  between  42°  and 
43°,  no  spore-formation  occurs,  although  at 
other  temperatures  it  usually  takes  place  when 
the  species  finds  itself  under  threatening  in- 
fluences. If  the  cultures  are  allowed  to  remain 
for  some  time  at  this  high  temperature  the  viru- 
lence, that  is  to  say  the  power  of  causing 
anthrax  in  animals,  decreases.  According  to 
Chauveau,  Koch,  and  Gaffky  and  LofHer,  20 
days  of  exposure  at  42°,  about  six  days  at  43°, 
3-4  hours  at  47°,  or  15-20  minutes  at  5o°-52°, 
produces  a  uniform  degree  of  attenuation. 
Similarly,  some  endospores  are  so  affected  by 
temperatures  of  8o°-ioo°  that  the  vegetative 
forms  to  which  they  give  rise  have  lost  their 
original  ability  to  excite  fermentation  or  dis- 
ease. Fitz  I  established  this  fact  for  the  bacillus 
of  butyric  acid  and  Arloing  and  Kitt 2  later  for 
the  bacillus  of  symptomatic  anthrax. 

It  is  possible  to  make  use  of  this  varying  be- 
havior to  temperature  to  obtain  pure  cultures. 
If  in  a  mixture  of  different  kinds  of  bacteria  or 
of  bacteria  with  other  organisms  the  endospores 
of  bacteria  are  present,  these  are  sure  to  be 
much  more  resistant  than  the  other  organisms. 

1  Ber.  der  Deutsch.  chem.  Gesellsch.,  1882,  p.  867. 

2  Centralbl.  f.  Bakt.,  III.,  1888. 


THE    VITAL   PHENOMENA    OF   BACTERIA.         67 

If  such  a  mixture  is  heated  these  other  organ- 
isms and  the  vegetative  forms  of  the  bacteria 
are  the  first  to  be  killed  ;  by  this  means  such 
spores  as  have  retained  their  vitality  can  be  sep- 
arated from  other  germs.  In  this  way  Roberts  ' 
secured  for  the  first  time  pure  cultures  of  the 
so-called  hay  bacillus  by  boiling  hay  infusion 
for  an  hour.  We  do  not,  to  be  sure,  always 
obtain  in  this  way  a  single  species  in  "  pure 
culture,"  but  simply  a  culture  of  all  those 
germs  which  happen  to  be  present  and  possess 
spores  of  approximately  equal  resistance.  So 
it  happens  that  under  the  names  "  hay  bacil- 
lus" and  " potato  bacillus"  are  commonly  in- 
cluded not  a  single  species  but  a  mixture  which, 
by  the  aid  of  other  methods,  may  be  resolved 
into  several  true  species. 

Sterilisation. 

By  selecting  temperatures  so  low  that  germs, 
cannot  develop,  putrescible  substances  can  be 
preserved  from  spoiling.  This  is  what  is  accom- 
plished by  the  use  of  ice,  by  refrigerating  cham- 
bers for  the  cold  storage  of  meat,  and  by  the 
chilling  of  milk.  For  effectual  conservation 
it  is  better,  however,  to  destroy  the  germs 
utterly.  This  process  of  making  a  sub- 
stance free  from  all  germs  is  generally  called 

1  Cf.  Zopf.  Die  Spaltpilze,  1885,  p.  74. 


68  BACTERIOLOGY. 

sterilization,  or,  in  the  particular  case  of  wound 
infection,  antisepsis.  A  term  commonly  used 
in  connection  with  infectious  diseases  or  epi- 
demics is  disinfection,  meaning  thereby  the 
destruction  of  infectious  matter.  A  tempera- 
ture of  over  100°  C  gives  the  surest  results. 
Pure,  air-free  steam  at  a  temperature  of  about 
120°  or  at  a  pressure  of  i^  atmospheres  is  ordi- 
narily employed,  since  no  bacterial  spores  are 
able  to  endure  its  action  for  more  than  half 
an  hour.  Streaming  steam,  free  from  air  but 
not  under  pressure  and  at  a  temperature  of 
about  100°,  can  also  be  used,  but  to  be  effective 
it  demands  a  longer  time.  Both  these  prin- 
ciples have  been  embodied  in  the  construction 
of  large,  stationary  pieces  of  apparatus  and  in 
small  transportable  devices.  By  means  of  these 
the  whole  technique  of  disinfection  has  been 
remodeled  and  such  processes  as  the  sterilizing 
of  milk  for  children  have  been  made  possible 
on  a  large  scale. 

For  other  purposes  we  are  able  to  reach  the 
same  end — only  somewhat  less  conveniently — 
by  long  boiling,  either  direct  or  in  a  water- 
bath.  It  is  often  necessary,  however,  as  our 
housewives  know  from  their  experience  in  the 
boiling  down  of  fruits,  to  repeat  the  heating 
operation  several  times  on  different  days.  This 
modification  is  called  intermittent  or  discon- 


THE   VITAL    PHENOMENA   OF    BACTERIA.  69 

tinuous  sterilization.  The  explanation  of  this 
process  was  first  given  by  Tyndall.  Many 
germs  resist  the  first  heating,  and  subsequently 
develop  in  the  favorable  nutrient  solution  ;  but 
the  germs  when  in  this  immature  condition  are 
less  resistant  and  hence  are  surely  destroyed  by 
a  second  application  of  heat.  This  method  is 
effective  even  when  carried  out  at  temperatures 
of  about  7o°-75°.  Such  temperatures  are  be- 
low the  coagulation  point  of  proteids,  and  hence 
blood  and  other  proteid-containing  fluids  such 
as  milk  and  beer  can  be  made  germ-free  by  dis- 
continuous heating,  although  their  proteids 
would  be  precipitated  by  the  temperature  of 
boiling  water.  The  use  of  temperatures  from 
65°-68°  in  such  cases  is  called  the  method  of 
pasteurization. 

The  resistance  of  bacteria  to  drying  is  devel- 
oped in  different  degrees,  and  depends  in  gen- 
eral upon  the  character  of  the  species,  the  extent 
of  zooglcea  formation  and  upon  the  presence  of 
spores.  Cholera  bacteria  vary  in  their  resist- 
ance to  drying  and  often  exhibit  differences  of 
from  a  few  hours  to  upwards  of  eight  months. 
Anthrax  spores  and  other  endospores  have  been 
found  to  be  still  capable  of  development  after 
remaining  in  a  dry  condition  for  ten  years. 
The  toxicity  of  cultures  slowly  desiccated 
in  the  air  decreases  more  or  less  rapidly,  as 


70  BACTERIOLOGY. 

Pasteur  first  demonstrated  for  the  bacteria 
of  chicken  cholera,  and  as  has  been  subse- 
quently ascertained  to  be  the  case  with  the 
pneumonia  and  cholera  germs. 

F.  Cohn  discovered  that  if  dry  hay  or  cotton 
waste  be  moistened  its  temperature  rises  and  a 
sort  of  fermentation  sets  in  which  rapidly 
raises  the  temperature  of  the  mass  to  67.2°. 
This  fermentation  is  caused  by  different  bac- 
teria, but  especially  by  a  species  of  micrococcus 
and  by  the  hay  bacillus.  In  Augsburg  high 
temperatures  produced  in  this  way  are  used  in 
the  heating  of  green-houses.  If  such  masses 
of  organic  substance  which  dampening  has 
caused  to  ferment  come  in  contact  with  any 
dry,  dust-like  material,  this  latter  may  burst 
into  flame.  Some  cases  of  "  spontaneous  com- 
bustion "  may  possibly  be  due,  therefore,  to 
bacterial  growth. 

As  regards  the  action  of  electricity  on  bac- 
teria, special  investigations  by  Kriiger1  have 
supplemented  the  earlier  works  in  which  stress 
was  laid  exclusively  upon  electrolytic  effects. 
According  to  Kriiger  the  constant  current,  when 
the  chemical  effect  of  the  ions  is  eliminated 
as  completely  as  possible  by  means  of  unpolari- 
zable  electrodes,  does  not  kill  bacteria  but 
does  completely  inhibit  their  growth.  If  the 

iZeitschr.  f.  klin.  Med.,  XXII.,  p.  191. 


THE   VITAL   PHENOMENA   OF   BACTERIA.         /I 

cooperation  of  the  ions  be  brought  into  play,  the 
constant  current,  when  of  sufficient  strength, 
intensity  and  duration,  is  able  to  destroy  both 
bacteria  and  their  spores.  The  electric  current 
acts  upon  toxic  bacterial  cultures  in  such  a  way 
as  to  remove  their  toxicity,  and  cultures  treated 
in  this  way,  with  their  toxic  power  destroyed, 
are  able  to  confer  immunity. 

Disinfection.      Effect  of  Poisons. 

The  behavior  of  bacteria  towards  chemical 
agents  has  been  much  investigated,  especially 
upon  practical  grounds,  in  order  to  obtain  dis- 
infectants against  disease  germs,  and  anti- 
septics against  the  germs  of  putrefaction.  The 
distinguished  military  physician  and  epidem- 
iologist Pringle  carried  out  experiments  in  the 
last  century  upon  the  action  of  disinfecting 
substances  on  infectious  material.  Unfortu- 
nately  a  period  of  crude  empiricism  followed, 
in  which  men  allowed  themselves  to  be  guided 
by  the  sense  of  smell  and  to  conclude  upon 
the  cessation  of  a  nauseous  stench  that  they 
had  destroyed  the  cause  of  the  disease.  Under 
the  sway  of  this  idea  sulphate  of  iron  obtained 
particular  favor  as  a  disinfectant,  and  among 
army  surgeons  the  fresh  whitewashing  of  rooms 
also  achieved  fame  as  a  method  of  disinfection. 


72  BACTERIOLOGY. 

The  first  to  establish  a  new  era  were  Semmel- 
weiss,  who  may  be  regarded  as  the  originator 
of  the  aseptic  method  of  treating  wounds  and 
who  recommended  the  use  of  chlorine  water  for 
cleansing  the  hands,  and  the  French  apothecary 
Lemaire,  who  recognized  the  fact  that  disin- 
fectants killed  microbes  but  did  not  alter 
unorganized  ferments.  Lemaire  found  that 
carbolic  acid  was  the  best  agent  for  disinfection, 
and  this  substance  was  later  brought  into  gen- 
eral use  by  Lister  for  the  antiseptic  bandaging 
of  wounds.  Jalan  de  la  Croix  and  Koch  after- 
wards brought  these  empirical  methods  to  the 
highest  point  of  efficiency  ;  Koch  clearly  distin- 
guished between  the  action  of  chemical  sub- 
stances upon  vegetative  stages  and  upon  rest- 
ing stages,  and  between  the  death  of  bacteria 
and  simple  inhibition  of  their  growth.  Both 
investigators  ascertained  that  the  poisonous 
substance  corrosive  sublimate  was  the  most 
effective  of  all  agents,  and  that  chlorine  was 
more  serviceable  than  carbolic  acid.  Accord- 
ing to  Koch,  anthrax  spores  were  prevented 
from  germination  by  the  presence  in  the 
nutrient  medium  of  corrosive  sublimate, 
T  :  300,000;  of  hydrochloric  acid,  i  :  1700  ;  of  sa- 
licylic acid,  i  :  1500  ;  of  potash  soap,  i  :  1000 ; 
carbolic  acid,  i  :  850 ;  quinine,  i  :  625  ;  alcohol, 
i :  12.5.  Only  a  few  substances  brought  about 


THE   VITAL    PHENOMENA   OF   BACTERIA.         73 

death  of  the  spores  inside  of  24  hours.  A  .2% 
solution  of  corrosive  sublimate  caused  death  of 
the  spores  inside  one  hour,  as  was  also  the  case 
with  a  .2%  solution  of  fresh  chlorine  water,  while 
other  agents  required  many  days  ;  a  5%  carbolic 
acid  solution  for  instance  needed  more  than 
forty  days.  On'  the  other  hand,  many  sub- 
stances caused  death  of  the  vegetative  forms 
in  the  course  of  a  few  minutes. 

A  better  understanding  of  these  processes 
was  arrived  at  when  it  became  recognized  that 
mechanical  purification  must  precede  disinfec- 
tion. Acids  and  alkalies  again  came  into  re- 
pute, and  it  was  found  that  strongly  concen- 
trated preparations  of  the  alkalies,  of  caustic 
soda,  of  quick-lime,  and  of  milk  '  of  lime  dis- 
solved in  water  (CaO+H2O=Ca  (OH)2)  were 
good  disinfectants,  and  indeed  that  common 
soda  itself  killed  germs  ;  that  a  direct  influence 
was  exerted  upon  the  proteid  of  the  bacterial 
cell  was  consequently  inferred.  For  the  same 
reason  the  acids  act  as  disinfecting  agents. 
Bacteria  are  more  susceptible  to  the  action  of 
the  mineral  acids,  like  sulphuric,  nitric  and  hy- 
drochloric acids,  than  to  that  of  the  vegetable 
acids  like  tartaric  and  citric,  and  least  suscep- 
tible toward  those  which  some  bacteria  them- 
selves produce,  such  as  acetic,  butyric  and 
lactic.  When  the  latter  are  formed  in  the 


74  BACTERIOLOGY. 

course  of  bacterial  growth,  development  of  the 
germs  ceases  when  a  certain  definite  proportion 
of  the  acid  in  solution  is  reached.  This  propor- 
tion has  been  accurately  determined  by  Hueppe 
in  the  case  of  lactic  acid,  and  a  similar  inhibiting 
point  has  been  shown  to  exist  in  the  case  of  the 
alcohol  produced  by  yeast.  If  the  lactic  acid  is 
neutralized  by  the  addition  of  carbonate  of  lime, 
fermentation  starts  up  again.  Prom  these  facts 
was  deduced  a  principle  of  immediate  practical 
importance,  viz.,  that  quick-lime  and  milk  of 
lime  are  disinfecting  agents  only  so  long  as 
sufficient  calcium  hydroxide  (Ca  (OH)2),  is  pre- 
sent. If  this  compound  is  converted  into  car- 
bonate of  lime  by  the  carbon  dioxide  of  the 
atmosphere  or  in  solution,  then  the  substance 
is  a  disinfecting  agent  no  longer,  but,  on  the 
contrary,  a  favorable  medium  for  bacterial 
vegetation  since  a  feebly  alkaline  reaction  of 
the  nutrient  medium  generally  favors  bacterial 
growth.  In  fruit  preserving,  again,  it  is  of 
interest  to  know  that  the  vegetable  acids  that 
are  present  check  bacterial  growth  but  permit 
the  vegetation  of  moulds. 

The  hydrochloric  acid  contained  in  the  gas- 
tric juice  constitutes  an  important  means  of 
defence  against  bacterial  invasion.  This  sort 
of  safeguard  is  not,  however,  developed  to  an 
equal  extent  in  different  individuals  and 


THE   VITAL   PHENOMENA   OF   BACTERIA.         75 

species  of  animals.  In  conditions  due  to  fast- 
ing, to  catarrh  of  the  stomach  and  to  overload- 
ing of  the  stomach,  the  amount  of  hydrochloric 
acid  present  does  not  suffice  for  protection,  so 
that,  to  take  an  example,  conditions  result- 
ing either  from  hunger  or  from  over-eating,  as 
well  as  from  diseases  of  the  stomach,  may 
facilitate  cholera  infection. 

Corrosive  sublimate  is  less  effective  as  a  ger- 
micide in  alkaline  fluids  containing  much  al- 
buminous substance  than  in  watery  solution. 
In  such  fluids  precipitates  of  albuminate  of  mer- 
cury are  formed  which  are  at  first  insoluble  so 
that  a  part  of  the  mercuric  salt  does  not  really 
exert  any  action.  If  these  albuminates  of  mer- 
cury are  dissolved  in  an  excess  of  blood  or  blood- 
serum,  they  become  very  effective,  and  Lister 
has  even  recommended  them  for  use  in  the  ban- 
daging of  wounds.  In  alkaline  solutions  such 
as  blood,  blood-serum,  pus,  tissue-fluids,  etc., 
the  soluble  compounds  of  mercury  are  converted 
into  oxides  or  hydroxides.  The  soluble  com- 
pounds can  of  course  remain  in  solution  only 
when  there  are  present  sufficient  quantities  of 
certain  bodies  which  render  solution  possible. 
Bodies  of  this  sort  are  especially  the  alkaline 
chlorides  and  iodides  and,  above  all,  sodium 
chloride  and  ammonium  chloride.  A  very  sim- 
ple way  of  preventing  precipitation  of  the 


76  BACTERIOLOGY. 

mercury,  then,  is  to  add  a  suitable  quantity  of 
common  salt  to  the  coirosive  sublimate.  Those 
compounds  of  mercury  which,  like  the  cyan- 
ides, are  not  precipitated  with  alkalies  because 
they  at  once  form  double  salts,  require  no 
addition  of  salt.  These  facts  were  recognized 
several  decades  ago  and  made  use  of  in  medi- 
cine, but  had  altogether  fallen  into  oblivion  un- 
til Liebreich  and  later  Behring  again  brought 
them  to  light.  The  double  salt  of  mercuric 
chloride  and  sodium  chloride  is  precipitated  by 
the  earthy  alkalies,  although  not  by  the  alka- 
line carbonates,  so  that  the  solution  should  be 
prepared  with  distilled  water  or  with  soft  water. 
Taking  into  consideration  the  matter  of  solu- 
bility, gold  and  silver  salts  such  as  potassium 
auri-cyanide  and  silver  nitrate  or. lunar  caustic 
are  very  powerful  antiseptics. 

Pure  carbolic  acid  or  phenol  (C6H5OH)  is 
soluble  in  water,  but  the  crude  carbolic  acid 
dissolves  only  with  difficulty.  For  this  reason 
various  means  have  been  devised  for  making 
the  commercial  acid  soluble  in  water.  Hueppe 
found  that  if  a  solution  was  prepared  with  sul- 
phuric acid  the  phenol  sulfonic  acids  which  arise 
through  the  replacement  by  HSO3  of  an  atom  of 
hydrogen  in  the  phenol  and  which  are  readily 
soluble  in  water  act  very  energetically  upon 
bacteria.  Under  the  name  of  aseptol  they  have 


THE   VITAL   PHENOMENA   OF   BACTERIA.         77 

come  into  practical  use  as  disinfectants.  Inci- 
dentally the  observation  was  made  (which  is  in- 
teresting as  regards  hypotheses  of  molecular 
constitution),  that  ortho-phenol  sulfonic  acid 
acts  very  strongly  upon  anthrax  spores,  but  that 
the  para-compound,  which  is  produced  by  heat- 
ing the  ortho-compound,  does  not.  The  differ- 
ence in  the  action  of  these  two  compounds  upon 
the  vegetative  cells  is  not  so  great.  Laplace 
prepared  mixtures  of  crude  carbolic  acid  and 
sulphuric  acid  which  were  very  active,  indeed 
more  active  when  they  were  made  in  the  cold 
than  when  made  at  a  higher  temperature. 
This  latter  fact  might  favor  the  view  that 
in  the  cold  the  real  ortho-sulfonic  acids  are 
formed,  while  at  the  higher  temperature  only 
the  less  active  para-sulfonic  acids  appear,  but 
might  also,  as  C.  Frankel  thinks,  be  explained 
on  the  supposition  that  in  the  cold  we  obtain 
only  mixtures  with  sulphuric  acids  ;  in  the 
warmth  real  sulfonic  acids.  Mixtures  are  in- 
deed, as  Rotter  first  showed,  often  more  effective 
than  the  individual  components,  but  Biel  has 
found  that  as  a  matter  of  fact  the  sulfonic  acids 
of  cresol  are  formed  in  the  cold.  It  is  an  im- 
portant fact,  however,  that  in  crude  carbolic 
acid,  cresol  (C6H4CH3OH),  as  well  as  phenol 
(CGH5  OH),  is  present  in  large  quantities.  Ac- 
cording to  C.  Frankel,  the  former  has  a  greater 


78  BACTERIOLOGY. 

disinfecting  power  than  phenol.  The  cresols 
are,  however,  so  difficultly  soluble  in  water 
that  their  action  is  not  sufficiently  powerful  to 
destroy  all  bacteria,  especially  the  spores. 

Since  solution  by  means  of  mineral  acids 
affords  strongly  corrosive  and  destructive  com- 
pounds, an  attempt  has  been  made  to  convert 
the  cresols  of  the  crude  carbolic  acid,  which 
are  almost  useless  for  purposes  of  disinfection 
because  of  their  slight  solubility,  into  a  form 
soluble  in  water,  in  order  to  utilize  thereby 
their  disinfecting  power.  Phenol  and  cresol 
are  easily  soluble  in  soap  solutions,  hydro- 
carbons difficultly  so.  If  we  start  with  a  coal- 
tar  oil  which  contains  much  hydrocarbon  and 
little  phenol,  and  mix  it  with  soap  and  dilute 
with  water,  an  emulsion  is  obtained  ;  this  is 
the  so-called  creolin.  If  on  the  other  hand 
we  take  first  a  coal-tar  oil  which  contains  little 
hydrocarbon  and  more  phenol  and  mix  this 
with  soap,  and  dilute  with  water,  we  obtain 
a  -solution  ;  examples  of  this  are  the  disinfect- 
ants sapocarbol  and  lysol.  Mixtures  of  crude 
carbolic  acid  and  soap  prepared  in  this  way 
turn  to  good  account  the  disinfecting  power  of 
cresol.  If  cresol,  which  is  by  itself  barely  sol- 
uble in  water,  be  mixed  with  the  difficultly  sol- 
uble salts  of  the  ortho-oxy-carbo-  or  ortho-oxy- 
sulfonic  acids,  the  mixture  is  soluble  in  water, 


THE   VITAL   PHENOMENA   OF   BACTERIA.         79 

both  of  the  difficultly  soluble  compounds  being 
rendered  easily  soluble.  Cresol  and  sodium 
salicylicate  taken  separately  are  likewise  diffi- 
cultly soluble  in  water,  but  are  readily  soluble 
when  mixed.  Sodium  cresotinate  is  for  this 
purpose  even  better  than  sodium  salicylicate 
and,  when  used  in  this  way,  the  resulting  sub- 
stances were  designated  by  me  as  solve ole ; 
they  are  neutral  and  not  corrosive.  Sodium 
cresol  is  more  easily  soluble  than  cresol  but 
somewhat  less  powerful,  just  as  sodium  phenol 
is  less  powerful  than  phenol.  A  large  quan- 
tity of  cresol,  however,  dissolves  in  sodium 
cresol,  so  that  we  can  obtain  watery  alkaline 
solutions  of  cresol  in  sodium  cresol  with  any 
required  percentage  content  of  cresol.  I  have 
called  this  preparation  solutol.  The  efficiency 
of  all  these  preparations  depends  partly  iipon 
their  cresol  content  which,  on  account  of  their 
solubility  in  water,  may  be  very  great  (cresol 
itself  is  soluble  to  the  extent  of  only  about 
.5 — i  p.c.in  water),  and  partly  upon  the  solvent. 
The  absolutely  neutral  solveol  is  therefore  a 
better  antiseptic  for  wounds  than  the  corrosive 
carbolic  acid,  and  contains  a  larger  quantity  of 
cresol  than  a  solution  in  water.  Lysol  emul- 
sifies fat  by  its  soaps,  while  the  alkaline  sol- 
utol penetrates  crevices,  saponifies  fats,  dis- 
solves proteid  bodies,  and  therefore  unites  the 


80  BACTERIOLOGY. 

disinfecting  power  of  cresol  with  the  purifying 
power  of  the  alkalies. 

Salicylic  acid  (C6H4COOH.OH),  is  also  a 
powerful  disinfectant.  The  structural  formulae 
of  the  substances  just  discussed,  phenol,  cre- 
sol, salicylic  acid  and  the  phenol  sulfonic  acids, 
prompt  the  conjecture  that  disinfective  power 
stands  in  relation  to  the  complexity  and  react- 
ivity of  the  atom  groups  in  the  molecule.  For 
we  may  anticipate  that  these  reactive  atom 
groups  can  interlock  with  and  upset  the  atom 
groups  of  the  unstable  proteid  molecule  more 
easily  than  can  less  mobile  atom  groups.  It 
might  be  fairly  expected  that  with  the 
entrance  into  chemical  bodies  of  such  atom 
groups  as  exalt  the  reactive  character  of  these 
bodies,  a  poisonous  effect  would  become  mani- 
fest. Phenol  or  mono-oxy-benzol  (C6H5OH), 
therefore,  should  be  less  poisonous  than  di- 
oxy-benzol  (C6H4(OH)2),  which  in  its  turn 
should  be  less  so  than  tri-oxy-benzol  (C6H3 
(OH)3).  Now  the  ortho-di-oxy-benzol  or  pyro- 
catechin,  the  analogous  meta-compound  or  re- 
sorcin,  and  the  paracompound  or  hydrochinon, 
are,  indeed,  to  be  regarded  as  poisonous,  but 
not  as  more  poisonous  than  phenol.  The  same 
thing  holds  true  of  the  tri-oxy-benzol s,  among 
which  pyrogallol,  oxy-hydrochinon  and  phloro- 
glucin  may  be  looked  upon  as  less  poisonous 


THE  VITAL  PHENOMENA  OF  BACTERIA.    8 1 

than  phenol.  Phenol  is,  however,  a  very  re- 
active body,  so  that  the  exception  is  only  ap- 
parent. 

Regarding  isomeric  bodies  the  chemically 
more  reactive  might  be  supposed  to  be  the  more 
poisonous.  For  example,  the  isonitriles  or 
isocyanides  or  carbylamine  whose  base  is  a 

hypothetical  isocyanic  acid  or   isoprussic  acid 

v 
of  the  formula  CN.H  (more  accurately  C=N-H, 

HI 

or,  according  to  others,  C=N-H)  ought  to  be 
more  poisonous  because  more  reactive  than 
the  nitriles  or  cyanides  whose  base  is  the 

prussic  acid  of  the  formula  H.CN  (more  accu- 

iii 

rately  N=C-H).  The  mustard  oils  which  are 
derived  from  the  hypothetical  iso-sulpho- 
cyanic  acid  (S.  CN.  H)  are  not  poisonous,  the 
sulpho-cyanates  which  are  derived  from  the 
sulpho-cyanic  acid  (S.  H.  CN)  are  poisonous. 
One  of  the  most  potent  poisons  known,  prussic 
acid  (H.  CN),  or  formic  acid  nitrile,  belongs  to 
the  nitriles.  It  is,  to  be  sure,  very  reactive, 
so  that  the  foregoing  exceptions  are,  perhaps, 
only  apparent.  These  examples  have  been 
chosen  in  order  to  show  that  we  are  but  just 
entering  upon  a  rigorous  scientific  conception 
of  the  nature  of  these  questions,  and  are  still 
at  the  beginning  of  the  development  of  laws. 


82  BACTERIOLOGY. 

Perhaps  the  exceptions  to  the  rule  above  noted 
may  be  explained  on  the  assumption  that  the 
molecular  structure  of  living  cells  has  led  to 
great  differences  in  the  structure  of  the  un- 
stable proteid  of  the  living  protoplast,  and  that 
chlorophyl-containing  and  chlorophyl-free  cells, 
as  well  as  the  various  cells  of  the  different 
organs  and  tissues  in  animals  and  plants,  pre- 
sent, through  adaptations,  variations  with  which 
the  atom  groupings  of  chemicals  have  to  reckon. 
It  is  true  in  general  that  disinfectants  whose 
action  upon  protoplasm  is  simply  that  of  a 
poison  do  even  more  damage  to  the  cells  of 
man  and  other  animals  than  to  the  bacterial 
cell.  In  spite  of  this  fact  the  internal  use  of 
an  antiseptic  substance  is  conceivable.  Beh- 
ring  has  found  in  the  case  of-  a  number  of 
chemical  substances  that  a  sub-cutaneous 
inoculation  of  approximately  one-sixth  part 
— reckoned  upon  the  weight  of  the  test  ani- 
mal— of  that  quantity  of  a  given  substance 
which,  in  blood-serum,  arrests  the  development 
of  the  anthrax  bacillus  certainly  kills  the  ani- 
mal and  that,  consequently,  inhibition  of  bac- 
terial development  and  poisorn  >us  action  upon 
man  and  the  lower  animals  go  hand  in  hand. 
But  apart  from  the  fact  that  we  cannot  yet 
make  a  universal  application  of  the  above 
rule,  the  experiments  made  up  to  this  time  indi- 


OF   TJ 


• 

V.  83 


THE   VITAL   PHENOMENA   OF   BACTERIA 

cate  that  the  property  of  inhibition  and  that  of 
disinfection  do  not  always  run  parallel,  just  as 
might  be  expected  from  the  fact  that  direct  cor- 
rosive effects  differ  from  phenomena  that  take 
place  in  blood  and  tissue  j uices.  Poisonousness 
is,  therefore,  only  relative.  From  this  point  of 
view  the  cresols  are  to  be  regarded  as  from 
two  to  four  times  as  strongly  disinfectant 
towards  some  bacteria  as  carbolic  acid,  or  from 
two  to  four  times  less  poisonous  than  carbolic 
acid.  That  is  to  say,  from  one-half  to  one- 
fourth  part  of  cresol  possesses  as  great  disin- 
fecting power  as  one  part  of  phenol.  Since 
both  bodies  are  equally  poisonous,  it  is  best  to 
use  the  smaller  amount  of  cresol  and  thus  to 
minimize  the  danger  from  poisoning.  Again, 
the  very  powerful  disinfectant  iodine  tri-chlo- 
ride  is,  according  to  Behring,  relatively  harm- 
less, since  at  the  beginning  of  the  disinfecting 
process  sodium  iodide  and  sodium  chloride  are 
formed.  As  early  as  1886  it  was  discovered 
also  that  the  ortho-phenol-sulfonic  acids  have 
just  as  strong  disinfecting  power  as  the  phenols ; 
they  corrode  less  and  are  not  so  poisonous. 

These  effects  are  in  the  line  of  specific  dis- 
infection, that  is  the  disinfectant  acts  more 
injuriously  upon  the  bacteria  than  upon  the 
cells  of  the  human  body.  It  is  perhaps  to  be 
remarked  as  an  advance  in  the  same  direction 


84  BACTERIOLOGY. 

that  we  successfully  administer  quinine  for 
malaria,  mercury  preparations  for  syphilis,  and 
salicylic  acid  for  rheumatism.  The  search 
after  similar  specifics  is  certainly  not  to  be  re- 
garded as  hopeless  when  it  is  remembered  that 
quinine  is  a  stronger  poison  for  the  lower  ani- 
mals or  for  the  algae  than  strychnine  or  mor- 
phine, while  with  the  higher  animals  the  re- 
verse is  the  case.  According  to  Donath,  chino- 
lin  is  harmless  for  yeasts,  but  is  a  poison  for  the 
bacteria  of  putrefaction. 

We  shall  see  that  in  a  way  to  be  considered 
later  the  aldehyde  group  (COH)  and  the  amido 
group  (NH2)  are  of  particularly  great  impor- 
tance in  the  construction  of  organic  substance, 
especially  proteid,  and  play  a  prominent  role 
in  the  activity  of  the  protoplasmic  proteids  of 
all  cells.  On  the  strength  of  the  foregoing 
fact,  Oscar  Low  predicted  and  then  proved  by 
many  experiments,  since  confirmed  by  other 
investigators,  that  all  substances  which  attack 
these  atom  groups  are  poisons,  since  they 
destroy  the  stability  of  the  active  proteid 
molecule  and  so  arrest  life.  Such  sub- 
stances, which  are  proved  to  be  poisons  for 
protoplasm  in  general,  must  be  also  poisons 
for  bacteria,  and  hence  suitable  for  purposes 
of  antisepsis,  disinfection  or  sterilization.  Ex- 
amples of  such  bodies  which,  even  in  great 


THE   VITAL   PHENOMENA   OF   BACTERIA.         85 

dilution,  attack  aldehyde  groups  and  whose 
poisonous  action  upon  protoplasts  and  bacteria 
has  been  proved  by  Low,  Marpmann,  and  H. 
Buchner,  are  prussic  or  •  hydrocyanic  acid 
(HCN),  diamid  (N2  H4),  hydroxylamine  (NH2 
OH),  phenyl-hydrazine  (C6H5)  'NH.NH2)  and 
sulphuretted  hydrogen  (H2S).  Similar  bodies, 
which  even  in  great  dilution  attack  amido 
groups,  and  whose  poisonous,  or  disinfecting 
qualities,  have  been  proved,  are,  according  to 
Low,  Buchner,  Kitasato  and  Weyl,  nitrous 
acid  (N2O3),  free  .cyanogen  or  dicyaiiogen 
(C2N2),  formaldehyde  (H.  COM),  acetaldehyde 
(CH3COH)  and  benzaldehyde  (C6H5.COH). 

Some  poisons,  as  for  example  alcohol,  may 
be  harmless  in  small  quantities  since  they  are 
easily  oxidized  in  the  presence  of  oxygen,  and 
others,  such  as  salicylic  acid,  indol  and  phenol, 
may  condense  or  unite  with  other  bodies  into 
non-poisonous  or  slightly  poisonous  products. 

The  connection  which  the  reactivity  of  atom 
groups  has  with  their  toxic  properties  is  shown 
also  by  the  fact  that  bodies  which,  in  a  given 
degree  of  concentration,  exert  no  injurious 
effect  upon  bacteria  at  .the  room  temperature 
(about  15°),  do  destroy  bacteria  when  the  tem- 
perature is  raised  to  37°,  and  still  more  cer- 
tainly if  it  be  raised  to  50°— 60°.  (Henle, 
Behring,  Heiden  and  Hammer  have  ascer- 


86  BACTERIOLOGY. 

tained  this  fact  for  anthrax  spores.)  The  high 
temperature  increases  the  amplitude  of  vibra- 
tion of  the  movable  atom  groups  within  the 
proteid  molecule  until  the  molecule,  at  the 
temperature  that  causes  rigor  and  death,  is 
rent  asunder  and  passes  over  from  the  condi- 
tion of  true,  active,  unstable  proteid  into  the 
state  of  rigid,  inactive,  dead  proteid.  That 
this  conception  is  in  reality  correct  follows 
from  the  fact  that  Scholl  was  able  by  treat- 
ment with  potash  to  restore  to  serum  albumin 
a  measure  of  the  activity  which  had  been 
arrested  by  heat. 

In  other  cases  the  active  proteid  appears  like 
an  anhydride  of  dead  proteid  ;  at  all  events,  on 
hydration  it  passes  over  into  an  inactive  con- 
dition. In  still  other  cases  the  active  proteid 
seems  like  a  polymerization  product  of  dead, 
inactive  proteid.  In  every  instance,  however, 
the  real,  living,  active  proteid  is  an  extraordi- 
narily complex  structure  as  contrasted  with  the 
inactive,  dead  proteid  with  which  alone,  until 
a  recent  date,  the  chemist  has  worked.  Such 
active  proteid  is  endowed,  through  the  reactiv- 
ity of  the  atom  groups  in  its  molecule,  with  nu- 
merous possibilities  of  movement.  Through 
communication  of  the  molecular  movements 
which  result  from  such  reactivity,  active  pro- 
teid may  on  its  side  affect  other  reactive  chemi- 


THE   VITAL   PHENOMENA   OF   BACTERIA.         8/ 

cal  bodies  and  other  reactive  proteids,  that  is, 
it  may  act  as  a  poison  or  disinfectant. 

The  action  of  the  so-called  unorganized  fer- 
ments or  enzymes  has  been  thought  for  a  long 
time  to  be  due  to  such  a  property.  Some  of 
these  enzymes  break  up  proteids,  fats  and  car- 
bohydrates by  hydrolytic  splitting ;  in  this 
way  albumoses  and  peptones  are  formed  out  of 
albuminates,  and  fatty  acids  and  glycerine  out 
of  fats.  For  example  : 

(C18H350)3C3H503  +  3H20  =  3Ci8H3602  +  C3H8O3 
tristearin,      water,  stearic  acid,          glycerine. 

and  : 

C44H90NP09  +  3H20  =  2C18H3602  H- 
lecithin,  water,         stearic  acid, 

C.H,POe  +  C5H15N02 
cholin, 

Examples  of  the  hydrolysis  of  carbohydrates 
have  been  already  tabulated  on  p.  34.  Other 
enzymes,  as  for  example  rennet  and  an  en- 
zyme found  in  the  blood,  bring  about  coagula- 
tion of  albumin.  Similar  effects  are  wrought 
by  bacteria,  and  enzymes  can  be  isolated  from 
the  cells  and  the  same  action  brought  about 
independently  of  the  living  bacteria  them- 
selves. Hueppe  and  Fermi T  have  demon- 
strated the  existence  of  bacterial  enzymes 
capable  respectively  of  fermenting  milk-sugar, 
of  bringing  about  hydration  of  starch,  of  co- 

1  Centralbl.  f.  Bakt.  VIL,  1889,  p.  449. 


88  BACTERIOLOGY. 

agulating  casein  and  of  dissolving  proteid. 
Kocli  has  made  use  of  the  ability  of  many 
bacteria  to  peptonize,  dissolve  and  liquefy 
gelatin  as  a  basis  for  the  separation  of  bacteria 
into  groups. 

Yet  more  remarkable  is  the  fact  that  active 
blood-serum  and  active  tissue  juices,  fresh  milk, 
etc.,  possess  the  ability  to  kill  bacteria  and 
sometimes  display  extraordinary  activity  in  this 
direction.  H.  Buchner  was  the  first  to  recog- 
nize and  demonstrate  this ;  he  was  able  by 
heating  these  substances  to  6o°-7o°  to  annul 
their  effect.  Behring  next  recognized  that 
active  blood-serum  can  nullify  the  effect  of  bac- 
terial poisons.  The  addition  of  carbolic  acid, 
thymol,  cresol,  toluene,  or  chloroform,  partially 
preserves  the  activity  of  these  'body-fluids  as 
it  does  that  of  enzymes.  Certain  of  these 
active  proteid  bodies  act  precisely  like  enzymes, 
so  that  between  the  newly  discovered  group 
and  the  old  no  sharp  line  of  demarcation  can  be 
drawn.  When  carefully  dried,  both  groups  of 
substances  withstand  high  temperatures,  while, 
in  a  moist  condition,  their  power  is  destroyed 
by  heating.  Many  of  the  "  specific  "  bacterial 
poisons  belong  to  this  group  of  enzymes  and 
active  proteid  bodies. 

Behring  was  the  first  to  recognize  that  one 
substance  ordinarily  alleged  to  be  an  effective 


THE   VITAL   PHENOMENA   OF   BACTERIA.         89 

antiseptic,  the  villainously  smelling  iodoform, 
is  in  reality  effective  as  an  antiseptic  only  when 
iodine  is  split  off — which  is  somewhat  unusual 
— and  that,  as  a  rule,  its  action  is  simply  to 
annul  the  effect  of  the  bacterial  poisons.  In 
this  connection  it  may  be  said  that  I  have  found 
that  the  bismuth  salt  of  tribromphenol,  which 
has  little  odor,  and  in  combination  none  at  all, 
and  which  is  a  powerful  disinfectant,  is  able 
to  destroy  bacterial  poisons  far  better  than 
iodoform. 

Of  great  interest  is  the  discovery  by  Naegeli x 
of  the  fact  that  a  mere  trace  of  metallic  copper 
proves  fatal  to  algal  protoplasm  ;  such  an  action 
is  called  by  him  "  oligodynamic."  Similarly, 
Miller  and  Behring  have  found  that  metallic 
gold  and  copper  can  arrest  the  development  of 
bacteria,  although  no  perceptible  trace  of  the 
metals  goes  into  solution.  Leaving  out  of 
consideration  for  the  moment  such  phenom- 
ena, which  are  as  yet  but  little  understood, 
as  well  as  the  fact  that  certain  chemical 
bodies,  even  when  in  extreme  dilution,  attack 
atom  groups  essential  to  the  vitality  of  liv- 
ing proteid,  a  generally  valid  conclusion  for 
the  effect  of  chemicals  upon  protoplasts  may 
still  be  drawn.  Arndt,  Schultz,  and  Hueppe 
have,  independently  of  one  another,  formu- 

1  Cf.  Biol.  Centralbl.  XIV.,  p.  129. 


90  BACTERIOLOGY. 

lated  a  biological  law  to  the  effect  that  every 
chemical  substance  which,  in  a  given  concen- 
tration, destroys  the  life  of  protoplasm,  and  in 
smaller  quantity  checks  development,  acts 
when  in  still  smaller  proportions  (on  the  other 
side  of  an  indifferent  point)  as  a  stimulus  and 
increases  the  vital  manifestations. 

In  agreement  with  the  above  statement  is 
the  fact  ascertained  by  Chamberland,  Roux 
and  Phisalix,  that  it  is  possible,  by  adding  a 
certain  quantity  of  carbolic  acid  or  chromic 
acid  to  anthrax  cultures,  to  destroy  the  spore- 
forming  property  of  the  germs,  and  to  diminish 
their  virulence  or  attenuate  them  to  a  definite 
extent.  Smirnow  and  Fliigge  have  shown 
that,  in  general,  attenuated  microbes  are  less 
resistant  to  chemical  influences  than  virulent 
cultures.  For  example,  the  virulent  anthrax 
bacillus  grows  well  with  the  addition  of  four 
drops  of  2  p.c.  hydrochloric  acid  to  the  nutrient 
gelatin,  but  the  growth  of  a  slightly  attenu- 
ated bacillus  in  presence  of  the  same  quantity 
of  acid  is  much  retarded  and  a  highly  attenu- 
ated germ  does  not  grow  at  all.  Hammer  has 
found  that  when  pathogenic  bacteria  are  at- 
tenuated the  virulence  of  the  spores  is  impaired 
before  their  power  of  development  has  suffered, 
and  Behring  has  even  obtained  growth  after 
the  spores  have  lost  all  power  to  kill. 


THE    VITAL   PHENOMENA   OF  BACTERIA.         9! 

Chemistry  of  the  Nutrient  Substratum. 

Up  to  a  few  years  ago  it  was  considered  an 
unimpeachable  tenet  of  biology  that  only  the 
plants  possessing  leaf-green  or  chlorophyl  are 
able  to  decompose  carbon  dioxide,  by  setting 
free  the  oxygen  and  utilizing  the  carbon  in  the 
construction  of  cell  substance,  starch  or  sugar. 
The  energy  for  this  synthesis  is  afforded  by 
the  sun's  rays.  Plants  containing  no  chloro- 
phyl and  all  animals,  it  was  supposed,  lacked 
the  power  to  assimilate  carbon  dioxide.  The 
assimilation  of  carbon  dioxide  by  green  plants 
takes  place  through  the  synthesis  of  formal- 
dehyde out  of  water  and  carbon  dioxide  ;  sugar 
arises  out  of  the  formaldehyde  by  polymeriza- 
tion ;  multiplication  of  the  aldehyde  formula 
by  six  gives  the  empirical  formula  of  grape- 
sugar  : 

I.  H2C03  CH20  +  03 
carbonic  acid,              formaldehyde       oxygen 

II.  6CH2O        =        C6H12O6 
formaldehyde,  grape-sugar. 

Even  before  E.  Fischer's  remarkable  achieve- 
ments in  the  synthesis  of  the  carbohydrates, 
Low,  starting  with  formaldehyde,  had  suc- 
ceeded in  building  up  the  first  sugar,  called 
formose  (acrose),  out  of  its  elements.  Organic 
chemistry  has  now  accomplished  the  synthesis 
of  polysaccharides  like  maltose  and  dextrine 


92  BACTERIOLOGY. 

out  of  grape-sugar,  the  construction  that  is,  of 
complicated  compounds  of  sugar  with  other 
bodies.  For  examples  of  the  decomposition  of 
maltose,  dextrine  or  starch,  I  may  refer  to  p.  52. 
The  following  illustration  of  the  decomposition 
of  glucosides  may  be  permitted  : 

C^H^NOn  +  2H20  '=  2C6H1206    +    C6H5.COH    +    HCN 
amygdalin,     water,     grape-sugar,    benzaldehyde,  prussicacid. 
C27H22017     +    4H20        =      C6H1306       +     3C7H605 
tannic  acid,         waterj          grape-sugar,  gallic  acid. 

According  to  ,  recent  synthetic  work,  the 
polysaccharides,  such  as  starch,  dextrine,  cane- 
sugar,  malt-sugar  or  maltose  and  milk-sugar 
are  to  be  regarded  as  glucosides  of  the  simple 
sugars.  In  this  connection  we  may  note  the 
interesting  fact  that  new  carbohydrates  may  be 
produced  from  other  carbohydrates  by  the  ac- 
tion of  prussic  acid,  and  that  prussic  acid  itself 
may  arise  also  as  a  decomposition  product.  We 
know  that  prussic  acid  (HCN),  one  of  the 
most  potent  of  the  nitrogenous  poisons,  under 
the  influence  of  polymerization  can  become 
non-poisonous  and  even  available  for  the  con- 
struction of  organic  substance,  as  Pfliiger  was 
the  first  to  demonstrate  :  for  example,  adenin,  a 
normal  element  of  the  cells  of  both  higher  and 
lower  organisms,  possesses,  according  to  its  dis- 
coverer Kossel,  the  formula  H5C5N5,  or  five 
molecules  of  prussic  acid  (5HCN).  According 


THE   VITAL   PHENOMENA   OF   BACTERIA.         93 

to  its  constitution  it  is  amidohypoxanthin 
C5  HA  N  H  N4  and  on  fusion  with  potas- 
sium, forms  potassium  cyanide  (KCN). 

Under  the  action  of  strong  hydrochloric  acid 
the  glucoses  also  form  polysaccharides,  such 
as  isomaltose  and  dextrine.  Through  the  com- 
bination of  synthetic  bodies  of  this  character 
with  ammonia  (NH3)  or  with  the  amido  group 
(NH2)  derived  from  it,  proteid  arises.  Accord- 
ing to  Oscar  Low,  the  following  formulae  in  a 
manner  express  the  conceptions  which  may  be 
formed  regarding  the  construction  of  proteid 
through  polymerization,  synthesis,  anhydride- 
formation,  reduction  and  condensation  of  the 
molecules  thus  originated.  Only  the  more 
important  intermediate  stages  are  considered. 

I.  H2CO3        =       CH2O       +       O2    (or  any  other  mode  of  form- 
carbonic  acid,     formaldehyde,  oxygen,     ation  of  formaldehyde). 

II.  4CH20     +     NH3  =  C4H7N02   +  2H3O 

formaldehyde,  ammonia,  aldehyde  of  aspartic  acid,  water. 

(i  e.  an  amido-acid. ) 

III.  3(C4H7N02)  =  C12H17N304   +  2H,O 

IV.  6(C12H17N304)  +  6H2  +  H2S  =  C72H112N18S022  +  2H2O 

simplest  expression  for  proteid. 

That  it  is  possible  to  pass  from  inert,  lifeless 
proteid  to  the  active,  living  proteid,  and  that 
Scholl  succeeded  in  one  case  in  making  again 
active  a  proteid  which  had  been  rendered  pas- 
sive through  heat  are  facts  already  mentioned. 


94  BACTERIOLOGY. 

Recently  Lilienfeld  and  Wolkowicz,  with  amido 
acetic  ethyl  ester  as  a  basis,  have  obtained  a 
kind  of  gelatin  peptone  and,  by  combination 
of  this  synthetic  body  with  the  ethyl  ester  of 
lencin  and  tyrosin,  have  built  up  a  sulphur- 
free  body  similar  to  proteid.  Ammonia,  that 
is  to  say  the  amido  group  NH2,  and  formalde- 
hyde are  looked  upon  as  the  first  members  of 
the  series.  We  are  now  able,  in  order  to 
make  clear  the  more  intimate  arrangement  of 
the  atoms  composing  formaldehyde,  to  write 
its  formula  CH.OH  or  to  use  the  arrangement 
H.COH  to  bring  out  the  aldehyde  group. 

If  we  possess  ammonia  for  a  source  of  nitro- 
gen we  may  expect  that  all  chemical  bodies 
which  contain  ready-made  formaldehyde,  or 
are  able  to  form  it  by  simple  rearrangement 
of.  the  atoms  can  serve  also  as  material  for 
the  synthesis  of  carbohydrates  or  of  the  nitro- 
gen-free group  of  proteids.  Experience  has 
confirmed  this  expectation  to  the  fullest  ex- 
tent, and  especially  is  this  true  of  those  bodies 
that  contain  the  groups  CH.OH  or  H.COH 
(that  is,  COH)  or  that  form  it  by  loss  of  hydro- 
gen (CH2OH— H  =  CHOH).  " 

I  may  call  attention,  however,  to  the  fact 
that  formaldehyde  itself,  as  already  mentioned, 
is  a  protoplasmic  poison,  since  in  the  free  con- 
dition even  in  great  dilution  it  attacks  amido 


THE   VITAL   PHENOMENA   OF   BACTERIA.         95 

groups,  but  that  in  combination,  as  for  in- 
stance with  sodium  sulphite  (Na2SO3),  it  loses 
its  poisonous  quality  and  can  serve  as  a  food 
for  protoplasm.  Pasteur  long  ago  established 
the  same  fact  in  the  case  of  tartaric  acid ;  the 
rule  holds  good  likewise  for  succinic  and  malic 
acids.  Neelsen  and  I  found  the  same  thing 
true  of  lactic  acid,  and  I  was  eventually  able  to 
make  quite  a  simple  solution  with  ammonium 
lactate,  in  which  the  bacteria  of  "  blue  milk  " 
form  synthetically  the  same  pigment  which 
in  milk  they  form  analytically.  (According 
to  Uschinsky,  cholera  and  diphtheria  germs 
also  form  synthetic  poisons  in  a  similar  solu- 
tion.) In  like  fashion  certain  sugars  may 
afford  fit  material  for  this  kind  of  synthesis. 

If  we  place  the  constitutional  formula  side 
by  side  with  the  empirical,  a  difference  becomes 
at  once  manifest  between  such  compounds  as 
tartaric  acid  or  malic  acid  which  contain 
CHOH  and  succinic  acid,  and  also  between 
lactic  acid  and  propionic  acid : 

Tartaric  acid     C4H6O6  ==  CHOH.COOH— CHOH.COOH. 
Malic  acid          C4H6O5  =  CHOH.COOH— CH2.COOH. 
Succinic  acid    C4H6O4  =  COOH.CH2  -CH3.COOH. 
Lactic  acid        C3H6O3  =  CH3— CHOH.COOH. 
Propionic  acid  C3H6O2  =  CH3— CH2— COOH. 

Whereas  tartaric,  malic  and  lactic  acids 
contain  the  group  CHOH  and  can  readily 
yield  formaldehyde  or  the  aldehyde  group 


96  BACTERIOLOGY. 

COH,  succinic  acid  and  propionic  acid  are  able 
to  yield  this  group  only  by  oxidation,  i.  e., 
CH2  +  O  =  CHOH.  The  former  bodies  are, 
as  a  matter  of  fact,  altogether  better  food-sub- 
stances for  bacteria  than  the  latter,  and, 
furthermore,  the  former  have  nutritious  value 
under  all  conditions,  and  especially  in  anaero- 
biosis,  while  the  latter  can  be  used  for  food 
only  in  the  presence  of  oxygen.  As  an  ex- 
ample of  the  utilization  of  such  substances, 
both  in  conditions  of  anaerobiosis  and  aerobio- 
sis,  tartaric  acid  may  be  instanced  (cf.  Low). 
In  the  absence  of  oxygen  : 

C4H6O6     =     2CH8O      +      H2        +        2CO2 
tartaric  acid,  formaldehyde,  hydrogen,  carbon  dioxide. 

In  the  presence  of  oxygen : 

C4H6O6    +    O    =    2CH2O     +     H2O     +     2CO2 

Nutritive  value  depends  therefore  upon 
purely  chemical  properties,  and  I  have  here 
indicated  one  aspect  of  the  matter.  Such 
bodies  as  have  little  nutritive  value  can  be 
utilized  only  with  the  aid  of  oxygen  because, 
when  they  break  up  without  oxygen,  they  can 
afford  neither  the  chemical  components  neces- 
sary for  the  construction  of  protoplasm  nor  the 
necessary  energy  for  construction  of  proto- 
plasm out  of  other  substances. 

I   have   previously  called  attention  to  the 


THE   VITAL    PHENOMENA   OF   BACTERIA.         97 

physical  point  of  view.  It  now  appears  clear 
from  chemical  considerations  that  in  anaerobi- 
osis,  oxygen,  to  speak  exactly,  is  not  taken  out 
of  the  molecule.  There  is  simply  an  atomic  re- 
arrangement by  means  of  which  the  hydroxyl 
radical  (OH)  effects  the  oxidation  of  the 
carbon  to  carbon  dioxide,  and  either  hydro- 
gen is  liberated,  or  reduction  products  rich  in 
hydrogen  arise,  or  the  hydrogen  combines 
with  sulphur  to  form  sulphuretted  hydrogen. 
The  instability  of  the  atom  grouping  is  there- 
fore the  real,  primary  reason  for  the  breaking 
up,  and  this  process  is  in  certain  cases  inde- 
pendent of  oxygen  and  can  therefore  proceed 
anaerobiotically. 

The  result  is  similar  if  a  chemical  body  con- 
tains within  its  own  structure  the  elements  of 
formaldehyde  and  ammonia.  Such  a  body  for 
instance  is  asparagin,  which  is  the  amide  of 
amido-succinic  acid,  and  hence  contains  nitro- 
gen which  can  be  utilized  in  the  same  way  as 
that  of  ammonia.  Asparagin  contains  also  the 
raw  material  of  formaldehyde.  Asparagin  is 
aspartic  acid  monamide  (C4H8N2O3  =  CH2. 
CONH2.CHNH2.COOH),  in  which  the  hy- 
droxyl OH  in  the  carboxyl  group  COOH  is 
replaced  by  the  amido  group  NH2,  and  an  H 
in  the  group  CH2  is  replaced  by  NH2.  A  part 
of  the  synthetic  work  therefore  is  already  ac- 


98  BACTERIOLOGY. 

complished  in  the  existing  condensation  of  the 
molecnle.  Asparagin,  as  compared  with  form- 
aldehyde and  ammonia,  is  one  degree  nearer  to 
proteid.  Conversely,  asparagin  arises  out  of 
proteid  through  oxidation.  Schiitzenberger 
by  artificially  decomposing  proteid,  obtained  a 
body  related  to  succinic  acid  which  had  the  em- 
pirical formula  C4H7NO2.  Low  considered  this 
body  as  formed  by  molecular  rearrangement  of 
the  hypothetical  aldehyde  of  aspartic  acid  or  of 
amido-succinic  acid  (C4H7NO4  =  CH2.COOH. 
CHNH2.COOH),  and  has  represented  its  prob- 
able significance  in  the  building  up  of  proteid 
in  the  formula  already  given  (p.  93).  Accord- 
ing to  Low's  conception,  the  chemical  basis  for 
the  reactivity  of  active  proteid  lies  in  the  associ- 
ation side  by  side,  as  shown  in  -  the  foregoing 
formula,  of  the  very  reactive  aldehyde  and 
amido  groups.  For  this  reason,  also,  all  those 
bodies  which  attack  these  two  groups  are 
protoplasmic  poisons  (cf.  p.  85).  It  has  been 
.ascertained  by  Neelsen,  Naegeli  and  Hueppe 
that  asparagin  is  one  of  the  best  substances  for 
the  nutrition  of  bacteria,  and  that  these  organ- 
isms can  construct  out  of  it  organic  pigments 
and  also,  as  Uschinsky  has  lately  determined, 
proteid-like  poisons.  The  nutritive  value  of 
asparagin  is  such  that  even  some  warm-blooded 
animals,  such  as  cattle,  can  make  use  of  it  to 


THE   VITAL   PHENOMENA    OF   BACTERIA.         99 

a  certain  extent  as  a  poor  substitute  for  pro 
teid  ;  gelatin  is  the  lowest  substance  of  the 
kind  utilizable  by  man. 

The  facts  of  fermentation  became  in  Pas- 
teur's hands  the  starting-point  for  conceptions 
which  later  were  to  revolutionize  our  way  of 
looking  upon  the  composition  of  chemical 
bodies.  Pasteur  found  that  in  certain  fermen- 
tations there  was  present,  besides  the  active 
dextro-rotatory  tartaric  acid,  the  so-called  active 
Isevo-rotatory  tartaric  acid.  These  two  acids 
combine  to  form  the  optically  inactive  racemic 
(paratartaric)  acid.  Pasteur  accounted  for  this 
by  the  asymmetric  structure  of  the  chemical 
molecule.  Out  of  this  beginning  Le  Bel  and 
van't  Hoff  developed  the  theory  of  the  asym- 
metric carbon  atom  and  modern  stereo-chemis- 
try. In  spite  of  all  the  progress  that  has  been 
made  in  developing  synthetic  methods,  the  de- 
struction of  inactive  substances  by  fermenta- 
tion and,  by  that  means,  the  preparation  of  the 
optically  active  components  has  been  held  to 
as  a  rapid  and  important  method  in  the  domain 
of  organic  chemistry  and  still  maintains  this 
position.  Schardinger  discovered  by  this 
method  the  laevo-rotatory  lactic  acid  which  had 
never  before  been  obtained  chemically,  and  the 
existence  of  which  was  suspected  only  because 
the  inactive  lactic  acid  and  the  active  dextro- 


100  BACTERIOLOGY. 

rotatory  lactic  acid  were  known.  In  this  con- 
nection it  is  also  worthy  of  note  that  bacteria, 
yeasts  and  moulds  exert  a  selective  power  in 
their  action  upon  inactive  bodies.  If  either 
yeast  or  the  common  blue-green  mould  (Pen- 
idllium glaucum)  is  fed  upon  racemic  acid,  that 
is,  upon  a  mixture  of  right  and  left-handed  tar- 
taric  acid,  the  right-handed  tartaric  acid  is  used 
up  and  the  left-handed  remains  behind  ;  the 
same  is  true  with  methylpropylcarbinol  and 
leucin.  If  the  mould  acts  upon  inactive  amyl- 
alcohol  or  amygdalic  acid,  the  left-handed  modi- 
fication is  consumed  and  the  right-handed  is 
left  untouched,  while,  if  dealt  with  separately, 
the  latter,  which  is  not  attacked  in  the  mixture 
or  inactive  compound,  can,  when  alone,  serve  as 
nutriment  to  the  mould  and  be  consumed  by  it. 
The  laevo-rotatory  fruit-sugar  as  well  as  the 
dextro-rotatory  grape-sugar  is  broken  up  by 
yeast  in  the  alcoholic  fermentation  ;  in  a  mix- 
ture of  both,  such  as  occurs  in  the  invert-sugar 
-of  honey,  the  grape-sugar  is  fermented  and 
the  left-handed  fruit-sugar  remains  unfer- 
mented.  The  same  thing  happens  in  a  mix- 
ture of  the  right-handed  galactose  derived  from 
milk-sugar  with  fruit-sugar,  and  this,  in  spite 
of  the  fact  that  when  by  itself,  fruit-sugar 
is  attacked  by  most  yeasts  more  readily  than 
galactose.  The  different  geometric  arrange- 


THE   VITAL   PHENOMENA   OF   BACTERIA.       IOI 

merits  of  the  atoms  in  the  several  molecules 
only  becomes  manifest  through  the  behavior  of 
the  substance  in  fermentation. 

In  order  to  construct  a  molecule  of  given  con- 
stitution, however,  differing  amounts  of  energy, 
dynamically  considered,  must  be  expended  ac- 
cording as  the  union  of  atoms  be  strong  or 
feeble  ;  and  correlatively,  this  union  of  atoms 
can  according  to  its  firmness  with  greater  or 
less  ease  be  loosed  again.  If  we  consider  two 
sugars  of  the  same  group  and  similar  empirical 
composition,  such  for  example  as  the  hexoses 
or  sugars  containing  six  atoms  of  carbon,  all 
of  which  have  the  same  empirical  formula 
CGH12O6,  we  can  distinguish  these  as  aldehyde 
sugars  or  aldoses  (with  the  group  COH),  and 
as  ketone  sugars  or  ketoses  (with  the  group 
CO).  Thus,  for  example,  grape-sugar,  an 
aldose,  possesses  the  formula  CH2(OH). 
(CHOH)4.COH,  while  fruit-sugar,  a  ketose, 
has  the  formula  CH2(OH).(CHOH)3CO.CH2 
OH.  If  we  experiment  with  two  such  alde- 
hyde sugars  in  which  the  inner  stability  of  the 
molecule  depends  upon  the  opposite  positions 
of  certain  atom  groups,  as  is  seen  in  grape- 
sugar  and  galactose,  we  find  that  the  compara- 
tively unstable  grape-sugar  possesses,  accord- 
ing to  Stohmann,  a  greater  store  of  energy 
than  the  more  stable  galactose  ;  consequently 


102  BACTERIOLOGY. 

less  energy  is  needed  to  topple  over  the  mole- 
cule of  grape-sugar  than  the  molecule  of  galac- 
tose.  Grape-sugar,  also,  according  to  experi- 
ments which  I  have  made,  is  more  easily  fer- 
mentable by  yeasts  than  galactose,  so  that 
here  also  a  choice  of  food-material  occurs,  the 
physical  reason  for  which  can  be  foreseen  in 
the  structure  of  the  molecule.  The  same  thing 
is  true  also  among  the  so-called  ketone  sugars 
or  ketoses  ;  among  the  hexoses  belonging  to 
this  group,  the  more  unstable  fruit-sugar  pos- 
sesses a  greater  store  of  energy  than  the  more 
stable  sorbinose  (Stohmann).  The  former  is 
easily  fermentable,  the  latter  difficultly  so. 
E.  Fischer  and  H.  Thierf elder l  have  lately  for- 
mulated this  principle  anew  and  have  ex- 
tended its  application  to  several  new  kinds  of 
sugars. 

The  celebrated  investigations  of  E.  Fischer 2 
upon  the  so-called  constitution  or  atomic  struc- 
ture of  the  sugar  molecule  require,  then,  for 
-their  full  comprehension  to  be  supplemented  by 
Stohmann's  investigations  on  the  dynamic  or 
energetical  relations  of  the  same  molecule,  and 
also  by  the  biological  facts  which  were  first 
established  by  Pasteur.  With  knowledge  of 

1  Ber.  d.  Deutsch.  Chem.  Gesellsch.,  XXVII.,  1894,  p.  2031. 

2  Ber.  d.  Deutsch.  Chem.  Gesellsch.,  XXIII.,  1890,  p.  2114,  XXVI., 
1894,  p.  3189- 


THE    VITAL   PHENOMENA   OF   BACTERIA.       103 

two  of  these  groups  of  facts,  indeed,  I  was  able 
some  time  since  to  infer  the  existence  of  the 
other  group  as  a  probable  contingency,  before 
such  existence  was  directly  ascertained.  I 
mention  this  only  to  show  how,  in  principle  at 
least,  the  biologist  is  at  no  disadvantage  in 
the  matter  of  accurate  prediction  as  compared 
with  the  physicist  or  astronomer.  His  method 
of  reasoning  is  just  as  precise  as  that  of  a 
mathematician,  but  his  material  is  for  the  most 
part  too  complex  to  admit  of  the  use  of  math- 
ematical signs.  The  demonstration  of  the  pos- 
sibility of  such  accurate  forecasting  establishes 
for  us  a  certain  security  as  regards  the  nature 
of  our  work.  The  unreasoning  pride  that  too 
often  hirks  in  a  onesided  mathematical  for- 
mula need  impose  upon  us  no  longer.  There 
is,  perhaps,  a  mathematics  without  the  usual 
symbols.  Far-seeing  physicists,  like  R. 
Mayer,  Helmholtz  and  E.  Mach,  have  already 
recognized  that,  in  order  to  be  intelligible, 
physical  observation  must  have  its  indispen- 
sable physiological  side.  In  the  monistic 
theory  we  possess  a  bond  uniting  not  only 
all  natural  sciences  with  one  another,  but  all 
the  natural  sciences  with  the  so-called  psycho- 
logical sciences. 

The  cells  of  those  animals  and  plants  that 
lack  chlorophyl  are  able,  according  to  the  cur- 


104  BACTERIOLOGY. 

rent  conception,  to  nourish  themselves  solely 
upon  organic  substances  by  the  breaking  down 
of  these  substances.  Dujardin,  however,  as 
far  back  as  1841,  discovered  that  bacteria  can 
build  up  their  body-substance  out  of  am- 
monium oxalate.  Oxalic  acid  is  C2H2O4  = 
COOH.COOH,  so  that  no  formation  of  for- 
maldehyde can  occur  through  a  simple  re- 
arrangement of  the  atoms.  With  the  forma- 
tion of  the  amido  group,  what  probably  happens 
is  that  since  the  oxalic  acid  in  question  is  an 
ammonium  salt,  a  reduction  by  the  hydrogen 
of  the  ammonia  occurs  : 

2NH3         =     2NH2     +         H2 
ammonia,     amido  group,     hydrogen. 

COOH.COOH     +     H2  CHOH     +     CO2     +     H2O 

oxalic  acid,  hydrogen,  formaldehyde.  , 

The  further  synthesis  of  proteid  can  after- 
wards proceed  out  of  the  formaldehyde  and  the 
amido  group. 

Again,  formic  acid  cannot  pass  over  into 
formaldehyde  simply  by  atomic  rearrange- 
ment, and  yet  O.  Low  has  made  the  important 
discovery  which  rounds  out  this  series  of  obser- 
vations, that  a  bacterial  species  which  can  turn 
formaldehyde  to  account  in  constructing  its 
oody-substance  can  also  make  use  of  formic 
acid.  Formic  acid  is  CH2O2.  Since  it  pos- 
sesses both  acid  and  reducing  properties  its 


THE   VITAL   PHENOMENA   OF   BACTERIA.       105 

constitutional  formula  can  be  written  either 
H.COOH  or,  to  express  its  relations  to  the 
aldehyde  group,  HO.COH. 

Compounds  that  contain  both  the  aldehyde 
group  COH  and  the  carboxyl  group  COOH 
are  aldehyde  acids.  We  can  therefore  write 
two  molecules  of  formic  acid  simply  2H.COOH 
or  2HO.COH,  or  we  may  also,  in  accordance 
with  the  reaction  in  which  it  takes  part,  conceive 
it  as  an  aldehyde  acid,  HO.COH— H.COOH. 
Within  an  organism,  different  sorts  of  reactions 
may  well  take  place  side  by  side  while  the 
chemist  is  able  to  determine  their  occurrence 
only  separately  in  separate  test-tubes.  The 
following  reactions  may  in  this  case  occur 
directly : 

I.  HO.COH          H.COOH  =  COH.COOH  +  H2O 
formic  acid,       formic  acid,     glyoxylic  acid. 

II.  COH.COOH     =    CHOH     +     CO2 
glyoxylic  acid,  formaldehyde. 

Glyoxylic  acid,  the  simplest  of  the  aldehyde 
acids,  may  be  an  intermediate  stage  between 
formic  acid  and  formaldehyde.  Konigs  has 
already  pointed  out  that  in  the  green  plants, 
glyoxylic  acid  arises  through  condensation  of 
two  molecules  of  formic  acid.  Formaldehyde 
might  be  obtained  also,  as  stated  above  to  bo 
the  case  with  oxalic  acid,  by  reduction  of  formic 
acid  : 


106  BACTERIOLOGY. 

H.COOH     +     H2     =     CHOH     +     H2O 
formic  acid,  hydrogen,  formaldehyde,  water. 

IIO.COH     +     H2     =     H.COH     +     H20 
formic  acid,  formaldehyde. 

From  formaldehyde  upwards  is  consummated 
the  synthesis  of  the  carbohydrates,  those  sub- 
stances devoid  of  nitrogen  which  are  an  im- 
portant constituent  of  proteid  and  are  funda- 
mentally alike  in  green  plants  and  in  organ- 
isms which  lack  chlorophyl. 

From  the  foregoing  statements  it  might  be 
taken  for  granted  that  formaldehyde  marks 
the  lowest  limit  at  which  chlorophyl-lacking 
organisms  are  able  to  begin  the  construction 
of  organic  substance,  and  that  nothing  but  the 
presence  of  leaf-green  or  chlorophyl  qualifies 
an  organism  for  the  assimilation  of  carbonic 
acid  in  combination  with  ammonia.  But  this 
limit  does  not  exist.  One  of  my  pupils, 
Heraeus,  made  the  observation,  the  signifi- 
cance of  which  he  did  not  at  first  grasp,  that 
even  bacteria  devoid  of  pigment  can  at  times 
nourish  themselves  with  ammonium  carbonate. 
This  power,  I  found,  occurs  only  among  the 
nitrifying  microbes,  which  are  able  to  oxidize 
ammonia  to  nitrous  and  nitric  acid.  I  ascer- 
tained further  that  it  is  this  combustion  of 
ammonia  that  furnishes  the  energy  for  the 
synthesis  and  assimilation  of  carbonic  acid  and 


THE   VITAL   PHENOMENA   OF   BACTERIA.       107 

that  the  process  is  carried  on  through  the 
utilization  of  formaldehyde.  Owing  to  this 
peculiar  method  of  obtaining  energy  the  pro- 
cess is  independent  of  light,  indeed  it  is  car- 
ried on  better  in  the  dark.  From  this  we  may 
recognize  the  fact  that  the  assimilation  of  car- 
bonic acid  is  a  physiological  property  of  all 
protoplasm,  and  that  the  chlorophyl  function 
is  an  adaptation  to  life  in  the  presence  of  light 
which  has  developed  out  of  simple  initial  stages. 
In  harmony  with  this  view  is  Pringsheim's 
theory  that  chlorophyl  is  only  a  physical  de- 
vice for  protecting  the  assimilating  cell-proto- 
plasm against  too  strong  sun-rays  which  would 
eventually  kill  unshielded  living  matter.  The 
injurious  action  of  light-rays  has  been  empha- 
sized by  bacteriology.  That  all  energy  is 
ultimately  derived  from  the  sun  is  a  fact  with 
which  the  development  of  individual  adapta- 
tions has  nothing  to  do  ;  in  view  of  the  vapor- 
ous atmosphere  that  prevailed  in  early  geologic 
times,  the  first  life  upon  the  earth  must  have 
existed  in  the  absence  of  direct  sunshine,  and 
only  later  could  it  have  adapted  itself  to  direct 
sunbeams.  A  connected  history  of  the  evolu- 
tion of  living  things  does  not  favor  the  con- 
clusion, which  the  early  botanists  could  not 
help  drawing,  that  chlorophyl  was  the  first 
created  of  organic  bodies. 


108  BACTERIOLOGY. 

In  harmony  also  with  the  above  facts,  is  the 
discovery  of  Engelmann  that  other  pigments 
besides  leaf-green  are  found  among  the  lower 
plants,  and  that  these  pigments  are,  like  chlo- 
rophyl,  qualified  by  their  physical  power  of 
absorption  to  aid  in  the  assimilation  of  car- 
bonic acid.  Such  pigments  are  found  among 
diatoms  and,  according  to  Engelmann,  the 
bacterio-purpurin  of  Beggiatoa  is  a  pigment 
of  this  character.  Chlorophyl,  which  has 
already  been  found  in  one  bacterial  species, 
the  Bacterium  chlorinum  of  Engelmann,  was 
merely  the  one  pigment  which  by  adaptation 
and  selection  became  favored  quantitatively. 
These  facts,  discovered  by  Pringsheim,  Engel- 
mann and  Hueppe,  and  the  views  advanced 
by  these  naturalists,  have  brought  about  a 
fundamental  broadening  of  the  scope  of  plant 
physiology. 

The  fact  that  nitrifying  bacteria  are  able 
to  utilize  not  only  ammonium  carbonate  but 
even  such  compounds  as  carbon  dioxide  and 
ammonia  was  confirmed  two  years  later  by 
the  Russian  investigator  Winogradsky,  and 
supplemented  in  important  particulars.  He 
was  greatly  mistaken  in  his  conception  of  the 
actual  chemical  process  of  synthesis,  however, 
since  he  thought  that  urea  was  formed  first, 
while,  in  reality,  urea  must  be  changed  into 


'THE   VITAL   PHENOMENA   OF   BACTERIA.       109 

ammonia  before  it  can  enter  into  the  proteid 
synthesis.  Frankland  and  Low  have  in  this 
connection  corrected  my  own  earlier  concep- 
tion. I  had  found  no  nitrous  acid  as  an  inter- 
mediate stage  and  had  therefore  supposed  a 
direct  oxidation  of  the  ammonia  to  occur : 

I.  NH3        -+-       202     =     HN03   +  H20 
ammonia,       oxygen,       nitric  acid. 

II.  C02        +         H20       =      H2C03      =      CH20     +    O2 
carbon  dioxide,  water,  carbonic  acid,  formaldehyde,  oxygen. 

while  Low  supposes  : 

I.  2NH3   +  2O2     =  2HNO2   +  2H2 
ammonia,     oxygen,     nitrous  acid,    hydrogen 

II.  C02         +         2H2       =      CH20     4-          H20 
carbon  dioxide,  hydrogen,    formaldehyde,     water. 

The  further  synthesis  of  carbohydrates  and 
proteids  is  carried  out  in  the  way  previous- 
ly stated.  Perhaps  the  possibility  of  both 
methods  of  oxidation  should  be  taken  into  con- 
sideration, for  I  at  least  entirely  overlooked 
the  nitrous  acid,  while  Winogradsky  now 
supposes  that  two  kinds  of  bacteria  exist, 
the  one  of  which  oxidizes  ammonia  only  as  far 
as  nitrous  acid,  and  the  other  oxidizes  nitrous 
acid  to  nitric  acid.  According  to  Winogradsky, 
the  oxidation  of  35.4  milligrams  of  nitrogen  is 
necessary  in  order  to  bring  i  milligram  of 
carbon  into  organic  combination.  The  matter 
has  a  practical  interest  since,  by  the  use  of 
material  which  contains  the  nitrifying  bac- 
teria as  a  fertilizer,  it  is  possible  to  increase 


1 10  BACTERIOLOGY. 

the  yield  of  many  kind  of  soils.  Burri  and 
Stutzer  claim  that  in  the  reduction  of  nitrate 
through  nitrite  to  ammonia,  two  kinds  of  bac- 
teria are  able  to  work  symbiotically. 

This  discovery  has  had  still  another  interest- 
ing consequence.  The  French  investigators 
Schlosing  and  Miintz  had  previously  cham- 
pioned the  view  that  microbes  play  a  role  in 
the  disintegration  of  rocks.  Since,  however,  it 
was  believed  that  chlorophyl-lacking  microbes 
were  not  able  to  assimilate  carbonic  acid,  which 
in  this  connection  might  possibly  be  regarded 
as  a  source  of  carbon,  they  supposed  a  source  of 
carbon  existed  in  alcohol  (!),  and  took  great 
pains  to  show  that  alcohol  is  an  uncommonly 
widely  distributed  product  and  occurs  every- 
where over  the  earth.  The  matter  was  novel 
and  the  argument  so  ingenious  that  serious 
German  periodicals  immediately  reported  it  to 
their  readers  without  heeding  the  derision  of 
every  sound  critic.  The  microbes  that  take 
part  in  the  disintegration  of  rocks  are  perhaps 
just  as  well  able  to  assimilate  ammonium  car- 
bonate as  those  nitrate-forming  bacteria  found 
in  the  soil  and  between  the  floors  and  ceilings 
of  our  dwellings.  Several  years  after,  the  ques- 
tion was  cleared  up  by  new  investigations,  and 
upon  the  appearance  of  Winogradsky's  work, 
Schlosing  and  Miintz  changed  their  views. 


THE   VITAL   PHENOMENA   OF   BACTERIA.       I  1 1 

Winogradsky  has  discovered  that  there  are 
other  sources  of  energy  besides  the  sun's 
rays  and  the  oxidation  of  ammonia  which  are 
available  for  purposes  of  organic  synthesis. 
He  found  that  the  iron  bacteria,  Crenothrix 
and  Leptothrix  ochracea,  which  sometimes 
bring  about  the  dreaded  "  water  calamity  " — 
as,  for  example,  that  in  the  Berlin  supply  from 
Lake  Tegel — can  obtain  their  energy  by  oxi- 
dation of  ferrous  compounds  to  ferric  com- 
pounds, as  e.  g.  from  ferrous  carbonate  to  ferric 
hydroxide  :  2FeCO3  +  3H2O+O  =  Fe2  (OH)6+ 
2CO2.  The  presence  of  iron  in  the  sheath  of 
Crenothrix  had  been  previously  recognized  by 
Zopf  as  a  phenomenon  probably  of  significance 
to  the  life  of  the  bacterium.  In  this  way  the 
iron  algae  and  the  iron  bacteria  share  in  the 
formation  of  the  phosphates  and  silicates  of 
iron  deposited  in  the  old  morasses,  and,  from 
this  point  of  view,  they  belong  to  those  mi- 
crobes concerned  in  rock-formation  and  the 
building  up  of  the  earth's  crust. 

The  Beggiatoa  or  sulphur  bacteria,  some  of 
which  are  devoid  of  pigment  and  some  colored 
by  bacterio-purpurin,  are  able  to  obtain  their 
energy  through  the  oxidation  of  sulphuretted 
hydrogen  and  then  of  the  sulphur  grains  thus 
formed  to  sulphuric  acid.  To  this  oxidative 
process  maybe  due  the  appearance  of  the  sul- 


I  12  BACTERIOLOGY. 

phur  grains  in  Beggiatoa  and  their  subsequent 
disappearance.  The  formation  of  sulphuretted 
hydrogen  by  the  breaking  up  of  proteid  or  by 
the  reduction  of  sulphates  is  accomplished  by 
various  kinds  of  bacteria ;  the  process  of  oxida- 
tion may,  be  considered  as  taking  place  in  two 
stages : 

I.  2H8S       +       O2   =  2H2O    +   S2 
sulphuretted  hydrogen. 

II.  S3     +    2H20   +    302    ==   2H2S04 
sulphur,  sulphuric  acid. 

The  process  of  the  reduction  of  sulphates  is  car- 
ried on  also  by  Beyerinck's  Spirillum  desul- 
furicans,  the  sulphuretted  hydrogen  being  able 
to  attack  the  iron  salts  with  consequent  forma- 
tion of  sulphide  of  iron.  In  this  case,  however, 
ammonium  carbonate  cannot  be-  utilized  for 
synthesis,  so  that  physiologically  we  are  here 
dealing  with  a  higher  stage  of  organization. 
Engelmann  suggests  that  intermediate  stages 
may  perhaps  be  found  among  the  splendid 
purple-red  Beggiatoa. 

Bacteria  take  part  in  yet  another  way  in  the 
formation  of  the  earth's  crust.  If  cellulose  be 
decomposed  by  bacteria  under  water  and  in  the 
absence  of  air,  not  only  acetic  acid,  butyric  acid 
and  carbonic  acid  are  formed,  but  also  hydro- 
carbons, methane  (marsh-gas  or  fire-damp)  and 
coal ;  bacterial  processes  of  this  nature,  then, 


THE   VITAL   PHENOMENA   OF   BACTERIA.       113 

mark  the  beginning  of  coal  formation.  Van 
Tieghem,  by  the  microscopic  examination  of 
coal,  has  shown  that  such  bacterial  relations 
really  do  exist : 

I.  2iC6H10O3     +    uH2O   =   26CO2    +    ioCH4     +      I2H 
cellulose,  water,  marsh-gas,  hydrogen 

+    I9C2H4O2     +      i3C4H8O2 
acetic  acid,  butyric  acid. 

II.  C6H1005     +   4H20     =     3Cp2     +     3H20    +  4H2     + 

cellulose,       water,    carbonic  acid,    water,     hydrogen, 
C3H4 
hydrocarbon. 

III.  C3H4      +      2H2    =    C      +      2CH4 
hydrocarbon,  hydrogen,  coal,    fire  damp. 

Gintl  looks  npon  the  carbonic  acid  developed 
by  this  process  as  the  chief  sonrce  of  the  car- 
bonic acid  occurring  in  natural  mineral  waters 
which  are  derived  from  strata  of  moor-coal  or 
bituminous  coal. 

Blach stein1  has  discovered  that  various  inor- 
ganic salts  are  often  of  the  greatest  signifi- 
cance for  the  life  of  bacteria,  and  that  their  cor- 
rect selection  determines  whether  or  not  some 
of  the  disease-producing  bacteria  retain  their 
virulence.  Kiihne 2  and  yet  more  successfully, 
Proskauer 3  succeeded  in  bringing  about  growth 
of  the  tubercle  bacillus  by  taking  glycerin  or 
starch  as  the  basis  of  a  nutrient  solution  and 
adding  to  it  asparagin  or  ammonium  lactate, 
tartrate,  malate  or  even  oxalate.  Or  if  other 

1  Berl.  klin.  Wochenschr.,   1894,  No.  17. 

2  Zeitschr.,  f.  Biol.,  XXX.,  p.  239. 

8  Zeitschr.,  f.  Hyg.,  XVIII.,  p.  128. 


114  BACTERIOLOGY. 

sources  of  carbon  were  used,  other  nitrogen 
salts  might  be  employed. 

Bacteria,  then,  are  able  to  construct  their 
body  substance  out  of.  various  kinds  of  nu- 
trient materials  and  also  to  produce  the 
organic  pigments,  or  fermentation  products 
or  poisons  especially  characteristic  of  individ- 
ual species,  and  they  are  able  to  do  this  either 
analytically  or  synthetically  with  almost  equal 
ease.  This  ambidextrous  metabolic  power 
exists  among  bacteria  to  an  extent  known  as 
yet  among  no  other  living  things,  and  these 
organisms  consequently  occupy  physiological- 
ly even  more  than  morphologically  a  kind  of 
intermediate  place  between  animals  and  plants. 
We  know,  of  course,  that  every  animal  and 
plant  cell  works  analytically  as  well  as  syn- 
thetically and  that  the  earlier  abrupt  distinc- 
tion between  animals  and  plants,  according  to 
which  the  former  were  supposed  to  be  mechan- 
isms adapted  for  oxidation,  the  latter  mechan- 
isms for  reduction,  does  not  exist.  Neverthe- 
less, the  differences  between  the  two  groups 
are  considerable. 

Among  bacteria  themselves  differences  in 
this  respect  may  be  remarked.  While  cer- 
tain species  appear  able  to  work  synthetically 
just  as  easily  as  analytically,  there  are  some 
kinds  which  are  better  adapted  to  the  one  me- 


THE   VITAL   PHENOMENA   OF   BACTERIA.       115 

thod,  others  to  the  other.  In  the  decomposition 
of  dead  organic  substance,  a  process  which  in 
the  form  of  putrefaction  and  decay  is  an  inter- 
mediate link  in  the  cycle  of  animal  and  plant 
life,  certain  species  are  better  fitted  to  break 
down  the  complex  compounds  present  at  the 
start  while  others,  work  up  the  end  products. 
According  to  the  discoveries  of  Heraeus, 
Hueppe  and  Winogradsky  the  nitrifying  bac- 
teria are  best  fitted  for  the  last  part  of  the 
process  ;  and  the  iron  and  sulphur  bacteria 
stand  next  above  in  the  series. 

Through  the  beautiful  investigations  of  Hell- 
riegel  and  Wilfarth  we  know  that  in  the  root 
tubercles  of  the  Leguminosa  and  some  other 
plants,  bacteria  are  found  which  have  entered 
into  an  intimate  union  or  symbiosis  with  these 
plants.  By  their  aid  the  plants  are  able, 
even  when  growing  upon  poor  soil,  to  avail 
themselves  of  atmospheric  nitrogen  for  the 
synthesis  of  proteids,  while  their  chlorophyl 
enable  them  to  use  synthetically  the  carbon 
dioxide  of  the  atmosphere.  This  discovery 
has  been  turned  to  good  account  and  marks 
one  of  the  notable  advances  in  agriculture. 
By  inoculation  of  the  soil  with  material  con- 
taining the  bacteria  of  the  root  tubercles,  and 
likewise  by  cultivation  of  the  useful  plants  upon 
which  these  microbes  are  symbiotic,  the  yield 


1 16  BACTERIOLOGY. 

of  many  poor  soils  may  be  considerably  in- 
creased without  the  application  of  manure.  In 
Germany  Schulz  has  accomplished  this  profit- 
ably with  the  use  of  lupine.  In  order  to  main- 
tain the  existence  of  those  plants  which  are  not 
possessed  of  such  direct  bacterial  assistance, 
nitrogen  in  the  form  of  saltpeter  must  be  ar- 
tificially added  to  the  soil,  or  else  we  must  sup- 
ply manures  rich  in  organic  substances  and 
out  of  which  ammonia  can  be  produced  by  bac- 
terial decomposition,  the  ammonia  being  in 
turn  oxidized  to  saltpeter  in  the  soil  by  the 
nitrifying  organisms. 

When  ordinary  organic  substances  are  decom- 
posed, several  species  of  microbes  generally 
take  part  in  the  process,  some  species  working 
together  and  simultaneously.  This  cooperative 
activity  is  called  symbiosis.  In  the  process  of 
sake  manufacture  in  Japan,  a  mould,  Aspergil- 
IMS  Oryzcz,  first  inverts  or  converts  to  sugar  the 
starch  of  the  cooked  rice,  and  out  of  this 
sugar  a  species  of  bacterium  then  forms  lactic 
acid  and  a  yeast  alcohol.  According  to  Juhler 
this  yeast  is  perhaps  only  a  yeast  form  belong- 
ing to  the  Aspergillus  itself  and  not  another 
species.  In  the  manufacture  of  arrack  in  Java 
and  sake  in  China,  a  species  of  Mucor,  accord- 
ing to  Eijkmann,  furnishes  the  invert  ferment, 
while  the  fermentation  of  the  molasses  is 


THE   VITAL   PHENOMENA    OF   BACTERIA.       117 

caused  by  a  yeast  of  unknown  species  together 
with  a  branched  bacterium  (Fig.  22).  In  the 
preparation  of  the  Eurasian  beverage  kumiss 
out  of  mare's  milk,  and  the  drink  called  omeire 
made  out  of  cow's  milk  in  southwestern  Africa, 
a  bacterium  and  a  yeast  act  together,  producing 
lactic  acid  and  alcohol  out  of  the  lactose.  A 
true  cooperative  growth  occurs  also  in  the  case 
of  the  so-called  kephir  grains,  a  symbiotic 
union  of  yeast  and  bacteria  which  together 
accomplish  a  fermentation  of  the  milk-sugar 
of  cow's  milk  with  formation  of  lactic  acid  and 
alcohol ;  these  kephir  grains  have  been  arti- 
ficially cultivated  in  Caucasus  for  centuries. 
According  to  investigations  by  Duclaux,  Ada- 
metz,  Grotenfelt  and  Beyerinck,  there  are 
also  some  yeasts  which  can  form  both  alcohol 
and  lactic  acid  out  of  milk-sugar,  and  are 
therefore  able  to  produce  unaided  by  any  bac- 
terium the  alcoholic  fermentation  of  milk. 

When  different  species,  adapted  for  different 
processes,  follow  one  another  in  sequence  the 
phenomenon  is  called  metabiosis.  The  end 
members  of  this  series,  those  which  are  best 
adapted  to  the  beginning  and  those  best  adapted 
to  the  close  of  decomposition,  are  often  in  a  sort 
of  opposition  or  antagonism.  In  the  decompo- 
sition of  organic  matter,  such  an  opposition 
outwardly  exists  between  those  organisms  that 


Il8  BACTERIOLOGY. 

initiate  the  putrefaction  of  proteids  and  the 
synthetically-working  nitrifying  bacteria  ;  fre- 
quently also  an  antagonism  is  manifested 
between  pathogenic  bacteria  and  the  bacteria 
of  putrefaction.  Another  sort  of  antagonism 
may  be  said  to  exist  between  the  species  that 
live  with  and  those  that  live  without  oxygen, 
as  Pasteur  long  ago  proved. 

Active  Proteids,  Ptomains,  Leucomains. 

By  the  decomposition  of  proteids,  bodies  are 
formed  which  must  themselves  be  regarded  as 
proteids  and  which  are  powerful  poisons.  The 
effect  wrought  by  most  pathogenic  bacteria  is 
due  to  the  formation  of  poisons  of  this  nature. 
Toxic  albuminous  bodies  were  first  demon- 
strated by  Bruylant  and  Venneman  in  1884, 
then  in  1886  by  Weir-Mitchell  and  E.  T.  Rei- 
chert1  in  snake-venom,  by  Warden  and  Wad- 
dell  2  and  by  Sidney  Martin.3  Later  the  pres- 
ence of  such  bodies  was  demonstrated  in  plants 
by  Kobert  and  Stillmark,  and  in  1888  the 
'poisonous  quality  of  the  blood-serum  of  the  eel 
was  observed  by  Mosso.4  These  observations, 
which  seemed  to  contradict  everything  that  pre- 
viously and  with  reason  had  been  believed  in 

1  Smithsonian  Contrib.  to  Knowledge,  1886. 

2  Maly's  Jahresb.,  20,  313. 

3  Proc.  Roy.  Soc.,  May  22,  1890. 

4  Arch.  f.  Exper.  Pathol.  u.  Pharm.,  25,  in. 


THE   VITAL   PHENOMENA   OF   BACTERIA.       119 

regard  to  albuminous  bodies  as  nutrient  sub- 
stances, were  at  first  neglected,  and  were  even 
regarded  by  Brieger  as  gross  chemical  errors. 
Little  confidence  was  at  first  placed  in  the  idea 
of  the  existence  of  active  proteid  bodies,  al- 
though Pfluger  suggested  it  in  1875,  an(^  L6'w 
plainly  expressed  it  in  1887  ;  the  older  works 
upon  fermentation  were  allowed  to  lie  neg- 
lected. 

Nencki I  and  later,  but  much  more  thorough- 
ly, Brieger 2  and  Vaughan 3  succeeded  in  prepar- 
ing organic  bases  of  a  definite  chemical  compo- 
sition out  of  putrid  fluids,  putrid  meat,  fish, 
shell-fish,  old  cheese,  spoiled  milk,  and  out  of 
bacterial  cultures.  These  were  found  to  exert 
a  poisonous  effect  and  for  a  long  time  were 
looked  upon  as  the  true  bacterial  poisons. 
These  poisons  are  particularly  interesting 
since  they  may  be  present  in  the  decomposing 
cadaver  (hence  the  name  ptomain)  and,  in  con- 
sequence, have  to  be  taken  into  consideration 
in  questions  of  legal  medicine.  Or  they  may 
be  found  in  the  living  human  body,  and,  if  not 
made  harmless  by  breaking  up  and  oxidation, 
may  come  to  act  therein  as  self-poisons  or  leu- 
comains.  But  they  are  not  the  substances  to 

1  Jour.  f.  prakt.  Chemie  [2],  20,  p.  454. 

2  Untersuchungen  iiber  Ptomaine,  Berlin,  1885  an<^  1886. 

3  Trans.  Seventh  Int.  Congress  of  Hygiene,  3,  p.  118. 


120  BACTERIOLOGY. 

which  the  peculiar  poisonous  effect  of  bacteria 
is  to  be  ascribed. 

Over  fifty  such  ptomains  are  known  already, 
and  the  empirical  formula  of  each  made  out, 
and  among  them  are  some  whose  exact  chem- 
ical composition  is  established.  The  first  of 
these  bodies  to  be  separated  was  collidin 
(CsHuN),  obtained  by  Nencki.  Trimethyla- 
min  (C3H9N  =  (CH8)8N),  gives  an  odor  like 
herring  brine.  Especially  interesting  is  the 
substance  cadaverin,  which  was  separated  by 
Brieger  from  portions  of  decomposing  dead 
bodies  and  from  cholera  cultures,  by  reason  of 
the  fact  that  Ladenburg  prepared  it  syntheti- 
cally and  showed  it  to  be  pentamethylenedia- 
min  ( (NH2)2(CH2)5).  The  substance  methyl- 
guanidin  (C2H7N3  =  (NH)24C(NH8)CH8),  al- 
ready known  as  an  oxidation  product  of  creatin, 
was  also  isolated  from  decomposing  fluids  and 
from  bacterial  cultures.  The  cholin  group  is 
particularly  interesting.  Cholin  itself  (C5H15 
NO2),  arises  from  the  hydrolytic  breaking-up 
of  lecithin,  the  fatty  substance  found  in  brain 
tissue  and  other  nervous  tissue  (p.  87).  The 
constitution  of  cholin  is  trimethylethoxy-am- 
monium  hydroxide  ==  (CH2)2.OH.N(CH3)3.OH. 
From  the  brain  also  Liebreich  and  Bayer  sep- 
arated neurin  (C5H13NO),  and  Bayer  showed 
this  to  be  trimethylvinyl-ammonium  hydroxide 


THE   VITAL   PHENOMENA   OF   BACTERIA.       121 

•=  C2H3.N(CH3)3.OH.  Cholin  is  only  slightly 
toxic,  neurin  intensely  so.  Through  the  re- 
moval of  water  from  the  molecule  and  the  con- 
sequent molecular  rearrangement  the  slight!}' 
poisonous  body  becomes  intensely  poisonous  : 

C5H15NO2  —  H2O  =  C5H13NO. 
cholin,         water,          neurin. 

Bayer  also  artificially  converted  cholin  into 
neurin. 

By  the  oxidation  of  cholin,  there  can  be  pro- 
duced the  non-poisonous  beta'in  or  trimethyl- 
glycocoll  occurring  in  beet  juice,  and  the  high- 
ly toxic  muscarin,  found  by  Schmiedeberg  in 
a  poisonous  toadstool,  and  by  Brieger  in  cer- 
tain decomposing  substances : 

CgH^NOg  +  03  =  CgHnNOg  +  H2O. 
cholin,  betam. 

C5H15N02  +  O  =  C5H15N93. 
cholin,  muscarin. 

Upon  the  common  base  of  trimethylethyl- 
ammonium  hydroxide  the  structural  formulae, 
according  to  Vaughan,  are  capable  of  giving  an 
idea  of  the  actual  relationship  to  one  another 
of  these  non-poisonous,  slightly  poisonous,  and 
very  poisonous  substances : 

CH.OH  CH2  CO.OH  CH^.OH 

CH2  CH  CH2  CH.OH 

N(CH3)3OH     N(CH3)3OH       N(CH3)3OH      N(CH3)3.9H 
cholin,  neurin,  bstain,  muscarin. 

Frequently  referred  to,  also,  is  the  substance 


122  BACTERIOLOGY. 

spermin,  which,  according  to  Kobert,  is  iden- 
tical with  piperazin  or  diethylene  diimin  ( (NH)2 
(CH2)4).  Poehl,  however,  disputes  this  identity 
and  ascribes  to  the  substance  the  formula  (C5H14 
N2)x.  The  substance  tyrotoxicon,  discovered 
by  Vaughan  in  cheese,  seems  to  be  derived  from 
butyric  acid  or  butyl-aldehyde. 

It  is  a  curious  fact  that  a  colored  alkaloid  base 
or  ptoma'inic  pigment  has  been  discovered,  the 
so-called  pyocyanin  (Ci4H14N2O),  which  pro- 
duces the  color  of  blue  or  blue-green  pus  and  has 
been  regarded  by  Ledderhose  as  related  to  the 
coal-tar  products.  Similar  bodies  of  a  basic 
nature  may  be  found  in  the  intestinal  contents 
as  the  products  of  bacterial  decomposition. 
Some  of  these  are  poisons,  and  can  be  absorbed 
into  the  body,  where  they  play  the  role  of 
self-poisons  or  leucomains.  Perhaps  the 
symptoms  designated  as  coma  and  tetany  may 
be  ascribed  to  something  of  this  nature. 
Katabolic  products  also  sometimes  originate 
in  the  body  which  may  accumulate  in  great 
quantities,  and  produce  auto-intoxication  and 
fatigue.  Some  of  these  substances  are  related 
chemically  to  the  ptomai'ns. 

In  some  cases  of  poisoning  due  to  decompos- 
ing meat  or  sausage,  or  to  cheese  or  milk, 
ptomai'ns,  according  to  researches  made  in  my 
laboratory,  may  not  be  concerned  at  all,  or  if 


THE   VITAL   PHENOMENA   OF   BACTERIA.       123 

so,  perhaps  only  secondarily,  and  other  bodies, 
the  poisonous  proteids,  may  be  the  real  cause. 
Such  poisonous  proteid  bodies  are  always 
formed  in  the  beginning  of  decomposition  pro- 
cesses. They  are  to  be  considered  as  "  active  " 
proteid  bodies,  having  in  part  an  enzymotic 
action,  and  their  activity  is  destroyed  by  high 
temperatures. 

Christmas  *  and  Hankin 2  were  the  first  to 
discover  that  pathogenic  bacteria  also  form 
such  primary  proteid-like  poisons,  or,  to  ex- 
press it  more  accurately,  form  poisons  which 
till  now  we  have  not  been  able  to  separate  from 
proteid  bodies.  These  bodies  likewise  are  to 
be  considered  as  active  proteids.  Here  belong 
the  poisons  of  diphtheria,  tetanus  and  cholera. 
The  activity  of  these  poisons,  too,  is  destroyed 
by  heating ;  and  the  active  proteid  changed 
to  the  passive  form. 

The  emphasis  is  to  be  laid  upon  "  active  " 
proteid  in  contradistinction  to  u  passive  "  pro- 
teid. The  classification  of  the  proteid  bodies, 
worked  out  by  Hoppe-Seyler  and  W.  Kiihne, 
has  hitherto  taken  into  consideration  only  the 
passive  proteid  bodies.  This  scheme  does  not 
include  the  "  active  "  proteids  which  we  know 
as  poisons,  and  under  such  a  classification  cer- 

1  Ann.  de  1'Inst.  Pasteur,  1891,  p.  487. 

2  Brit.  Med.  Jour.,  1889,  p.  810. 


124  BACTERIOLOGY 

tain  of  these  bodies  could  not  be  called  pro- 
teids  at  all.  To  illustrate,  if  certain  bacteria 
are  cultivated  upon  proteid-free  nutrient  media, 
such  as  ammonium  lactate  or  asparagin, 
poisonous  substances  are  usually  produced, 
but  proteid  reactions  are  not  always  obtained 
from  the  filtered  solutions.  On  the  other 
hand,  it  is  positively  established  that  the 
poison  always  constitutes  only  a  slight  frac- 
tion of  the  whole  solution.  In  solutions  con- 
taining proteid  there  is  always  some  poison 
side  by  side  with  much  proteid,  and  the  inten- 
sity of  the  reaction  has  often  been  falsely  at- 
tributed to  the  quantity  of  the  latter,  for  we 
know  of  no  chemical  method  by  which  we  are 
able  to  distinguish  between  the  poisonous 
active  proteid  and  the  non-poisonous  passive 
proteid  of  the  same  group.  A  very  slight 
amount  of  poisonous  proteid,  however,  in  an- 
other solution  may  elude  our  test  for  proteid. 
So,  for  example,  one  part  of  rennet  curdles 
two  million  parts  of  casein  ;  according  to  Vail- 
lard,  there  is  contained  only  0.0002  5  gr.  of  the 
solid  tetanus  toxin  in  a  dose  fatal  to  a  guinea- 
pig  ;  and  according  to  Kobert  and  Stillmark, 
0.00003  gr.  of  ricin  per  kilogram  of  body- 
weight  of  the  animal  is  fatal  when  injected 
into  a  vein.  Such  slight  quantities  may  well 
escape  the  coarse  reactions  of  proteid  chemis- 


THE   VITAL   PHENOMENA   OF    BACTERIA.       125 

try,  although  in  experiments  with  animals 
they  can  be  unmistakably  detected.  For  these 
reasons  we  can  and  indeed  must  make  our 
conception  of  these  poisons,  the  "  active  pro- 
teids,"  a  wholly  provisional  one.  They  are 
certainly  to  be  referred  to  the  coagulable  pro- 
teids,  and  are  less  resistant  to  heat  than  the 
poisons  belonging  to  the  group  of  albumoses 
and  peptones.  Their  extraordinary  "  activity  " 
recalls  that  of  the  enzymes,  and  for  this  rea- 
son Roux  has  considered  that  the  diphtheria 
poison,  and  Nencki  that  all  these  poisons  are 
of  an  enzyme  character.  But  to  regard  them 
as  enzymes  does  not  altogether  free  us  from 
difficulty.  The  fact  of  their  extraordinary 
activity  still  faces  us,  whether  we  call  these 
poisons  enzymes  in  the  earlier  limited  sense  in 
which  that  term  was  used,  or  whether,  on  ac- 
count of  our  more  extended  knowledge  of 
activity  on  the  part  of  proteid  bodies,  we  fall 
in  with  Nencki's  suggestion  and  widen  our 
conception  of  the  nature  of  an  enzyme. 

Effect  of  Bacteria  upon  the  Substratum. 

From  the  earliest  observers  (among  whom  I 
need  mention  only  Leeuwenhoek,  O.  F.  Muller, 
von  Gleichen-,Russworm,  Ehrenberg  and  Du- 
jardin)  of  "  infusion  animals,"  the  name  under 
which  for  a  long  time  bacteria  were  classed, 


126  BACTERIOLOGY. 

down  to  Ferdinand  Cohn,  Josef  Schroter  and 
Robert  Koch  there  have  always  been  investiga- 
tors who  supposed  a  rigid  constancy  of  form 
and  species.  These  observers,  moreover,  ' 
established  genera  and  species  as  had  been 
done  in  the  first  instance,  directly  according 
to  form,  and  thus  came  about  the  conception 
of  form-genera  and  form-species,  the  individual 
forms  of  which  were  supposed  to  be  always  the 
same.  So  long  as  this  idea  prevailed,  when- 
ever novel  forms  were  observed  after  an  alter- 
ation of  the  conditions  of  nutrition,  they  were 
referred  to  the  intrusion  of  germs  of  other 
species  ;  the  occurrence  of  unusual  fermenta- 
tive effects  was  also  taken  for  a  proof  that  for- 
eign germs  had  stolen  in.  Definite  forms  and 
uniform  effects  were  supposed  always  to  coin- 
cide. Under  the  influence  of  this  conception 
F.  Cohn  divided  bacteria,  according  to  the 
effects  they  produced,  into  pigment-forming  or 
chromogenic,  fermentation-provoking  or  zymo- 
genic  and  disease-producing  or  pathogenic. 
Thus  by  the  aid  of  physiological  characteris- 
tics, he  obtained  a  more  extended  application 
for  his  classification  into  form-species,  espe- 
cially as  regards  those  forms  that,  on  account 
of  their  minuteness,  did  not  admit  of  sharp 
distinction.  Many  of  the  species  thus  obtained 
are,  it  is  true,  collective,  and  with  more 


THE   VITAL   PHENOMENA   OF   BACTERIA.       1 27 

accurate  knowledge  have  been  resolved  into 
several  species ;  here  belong  for  example,  B. 
termo,  B.  subtilis  or  the  hay-bacillus,  B.  mes- 
entericus  or  the  potato-bacillus ;  to-day  such 
names  are  sometimes  used  in  a  general,  some- 
times in  a  limited  sense. 

At  first  stress  was  laid  upon  differences  and 
it  was  recognized  that  different  genera  and 
species  exist  among  bacteria  as  well  as  among 
the  Cyanophycea  or  among  the  moulds.  These 
discoveries,  which  were  supported  by  careful 
methods  devised  by  J.  Schroter  and  ingeniously 
extended  by  Klebs  and  especially  by  R.  Koch, 
formed  a  basis  for  all  subsequent  investigation. 
The  further  discoveries  of  J.  Schroter  and 
Hueppe  concerning  the  pigment  bacteria,  of 
Pasteur,  F.  Cohn,  Fitz,  Duclaux  and  Hueppe  re- 
garding the  processes  of  fermentation  and  decay, 
and  of  Davaine,  Pasteur,  R.  Koch,  Gaffky  and 
Loffler  in  regard  to  disease-producing  bacteria, 
established  bacteriology  upon  a  firm  founda- 
tion. 

It  was  supposed,  however,  in  the  beginning 
that  in  every  typical  fermentation  or  infectious 
disease  only  one  kind  of  micro-organism  was 
causally  concerned.  But  Mitscherlich  had 
even  then  discovered  that  the  yeasts  of  top  and 
bottom  fermentation  are  of  different  species, 
and  I  too  found  that  not  one  species  merely, 


128  BACTERIOLOGY. 

but  a  whole  series  of  bacteria  are  able  to  form 
lactic  acid  out  of  sugar ;  and  the  same  thing 
was  later  ascertained  in  regard  to  other  kinds 
of  decompositions.  In  the  lactic  fermentation 
the  kind  of  sugar  determines  the  nature  and 
course  of  the  process,  and  from  the  bacterio- 
logical point  of  view  it  might  almost  be  said 
that  every  germ  that  produces  lactic  acid  seems 
to  prefer  a  special  kind  of  sugar.  Hansen  has 
lately  found  a  new  germ  which  is  capable  of 
causing  the  oxidation  of  alcohol  to  acetic  acid, 
and  which  is  the  third  germ  known  to  possess 
this  power  as  two  others  had  been  previously 
discovered, — one  by  Kiitzing  and  one  subse- 
quently by  Pasteur. 

The  same  thing  has  been  shown  to  be  true 
of  the  power  to  produce  disease,  and  the  once 
prevalent  conception  of  "  specific  "  germs  of 
fermentations,  pigments,  and  diseases,  has  been 
completely  shattered. 

There  are  certain  well-known  fermentations 
evoked  by  bacteria,  the  chemical  side  of  which 
formerly  attracted  most  attention.  These  are 
especially  the  lactic  acid  fermentation  of  sugar, 
in  which  alcohol  and  acetic  acid  often  appear 
as  by-products  ;  the  alcoholic  fermentation  of 
sugar,  in  which  lactic  acid  is  always  produced 
as  a  by-product ;  the  butyric  acid  fermenta- 
tion of  sugar  and  lactic  acid  salts  ;  the  forma- 


THE   VITAL   PHENOMENA   OF   BACTERIA.       129 

tion  of  alcohol  and  butyric  acid  from  glycerin  ; 
the  viscous  fermentation  of  sugar  with  forma- 
tion of  gum  or  mannite ;  the  dextrine  fermen- 
tation of  carbohydrates  ;  the  viscous  fermenta- 
tion of  proteids ;  the  blue  and  red  coloration  of 
milk  (the  latter  may  be  due  to  different  causes) ; 
the  formation  of  blue  cheese  ;  the  fluorescence 
and  phosphorescence  shown  in  some  culture 
media  ;  the  production  of  ammonia  and  sul- 
phuretted hydrogen ;  and  the  formation  of 
nitric  and  acetic  acids. 

As  regards  the  occurrence  and  distribution  of 
bacteria,  it  may  be  said  in  general  that  these 
organisms  are  to  be  found  almost  everywhere. 
They  are  present  in  the  soil,  in  the  water  and 
in  the  air.  Differences  in  distribution,  however, 
do  occur.  In  the  upper  layers  of  the  soil  are 
found  not  only  enormous  numbers  but  many 
different  kinds  of  germs  favored  by  the  fluctua- 
tions in  humidity  and  by  the  varying  temper- 
ature. Here  in  the  ground  they  take  part  in 
the  decomposition  of  organic  substances,  and 
convert  these  to  ammonia,  oxidize  the  ammonia 
to  nitric  acid,  and  form  carbonic  acid  ;  indeed, 
we  may  look  upon  bacteria  as  the  most  impor- 
tant promoters  of  the  decompositions  called 
putrefaction  and  decay.  The  ground,  how- 
ever, acts  upon  bacteria  like  a  filter,  so  that  the 
number  quickly  diminishes  from  above  down- 


130  BACTERIOLOGY. 

wards,  and  the  ground  at  a  depth  of  from  four 
to  six  meters  is  germ-free.  From  the  soil  the 
bacteria  may  pass  into  the  water,  and  we  every- 
where find  in  water  the  same  germs  as  in  soil, 
unless  the  water  be  derived  from  the  deeper 
germ-free  layers.  In  water,  just  as  in  soil,  bac- 
teria share  in  the  decompositions  of  organic 
substance  and  aid  in  the  transformation  of  in- 
organic compounds  of  sulphur  and  iron.  In 
the  ooze  at  the  bottom  of  rivers  and  lakes, 
where  there  is  lack  of  oxygen,  they  bring  about 
the  formation  of  marsh-gas,  hydrogen,  and  sul- 
phuretted hydrogen,  and  so  take  the  first  step  in 
the  beginnings  of  coal-formation.  The  num- 
ber of  individual  germs,  and  of  species,  in  water 
and  soil  depends  largely  upon  the  amount  of 
decomposable  substances  present  in  the  sur- 
roundings. In  the  neighborhood  of  our  dwell- 
ings, in  the  tracts  of  low  land  about  rivers  and 
lakes,  and  in  river  deltas,  there  is  a  high  per- 
centage of  such  substances,  and  in  such  local- 
ities we  meet  active  decomposition  and  most 
luxuriant  bacterial  vegetation.  Many  species, 
like  B.  termo,  the  hay  bacillus,  and  the  earth 
bacillus,  are  apparently  spread  over  the  whole 
world,  others  are  very  rare  or  limited  to  special 
localities.  The  true  home  of  the  comma-bacil- 
lus of  Asiatic  cholera,  for  instance,  seems  to  lie 
in  the  notorious  Sunderbunds  of  the  Ganges. 


THE    VITAL    PHENOMENA   OF   BACTERIA.       131 

Other  foci  of  decomposition  probably  have  their 
own  bacteriological  peculiarities  which  make 
them'  the  home  of  special  germs.  The  germs 
causing  malignant  oedema  and  lockjaw  are 
often  found  in  the  earth  of  gardens.  I  once 
happened  to  find  the  extremely  rare  bacterium 
of  the  "  blood  portent "  (B.  prodigiosus]  in  a 
well  in  Wiesbaden.  Other  rare  species  occa- 
sionally appear  upon  our  nutrient  media  with- 
out our  being  able  to  ascertain  their  origin, 
and  then  fail  to  put  in  an  appearance  again  for 
years. 

In  general  the  germs  provoking  fermenta- 
tion and  disease  must  be  reckoned  among  the 
rarer  species.  This  is  true  at  least  in  so  far 
as  that  such  germs  generally  maintain  their 
power  only  if  they  have  frequent  opportunity 
to  evoke  fermentations  or  diseases.  Such 
opportunity  implies  the  existence  of  course, 
of  some  sort  of  industry  however  primitive, 
which  is  dependent  on  fermentation,  or  of  a  cer- 
tain aggregation  of  men  and  animals  on  which 
to  live. 

Even  a  very  rapid  flow  of  air  is  unable  to 
detach  a  single  bacterium  from  a  moist  sur- 
face, but  when  the  soil  or  the  margin  of  pools 
becomes  dried  up,  germs  may  pass  into  the  air 
along  with  the  dust ;  the  only  other  way  in 
which  bacteria  can  enter  the  air  is  through  the 


132  BACTERIOLOGY. 

spraying  of  water.  Bacteria  are  very  variously 
distributed  in  the  air  according  to  the  degree 
of  atmospheric  purity ;  their  number  decreases 
at  high  altitudes,  and  B.  Fischer  found  that 
the  air  over  the  sea  at  some  distance  from  land 
was  germ-free. 

Practical  Applications. 

Many  bacterial  discoveries  are  of  direct  prac- 
tical importance.  As  the  fermentation  indus- 
tries have  been  built  up  through  the  investiga- 
tions of  Pasteur  and  Hansen  upon  yeasts,  so 
the  fundamental  work  of  Duclaux  and  Hueppe 
upon  the  fermentations  of  milk  and  cheese  has 
paved  the  way  for  a  complete  revolution  in  the 
dairy  industry.1 

A  well-known  practical  result  of  bacterio- 
logical research  is  the  sterilization  of  milk. 
Before  the  discovery  was  made  that  it  is  possi- 
ble to  sterilize  milk  by  temperatures  below  the 
boiling  point  and  it  was  known  under  what 
conditions  this  could  be  done,  this  method  had 
been  declared  by  Pasteur  to  be  inapplicable  to 
milk,  and  its  impracticability,  as  was  thought, 
firmly  established.  Tyndall  is  largely  re- 
sponsible for  the  working  out  of  this  method  of 

1  To  forestall  the  criticism  that  this  conception  is  onesided,  it  is 
necessary  merely  to  mention  the  fact  that  other  important  improve- 
ments have  been  wrought  on  the  dairy  farm  by  the  introduction  of 
the  separator,  and  by  better  methods  of  housing  and  feeding  stock. 


THE   VITAL   PHENOMENA   OF   BACTERIA.       133 

pasteurization  as  it  is  called.  I  was  able  to  de- 
termine further  the  exact  temperature  at  which 
milk  can  be  made  germ-free  and  showed  that, 
in  order  to  obtain  milk  that  would  keep  and  re- 
main fit  for  transport,  a  temperature  of  120° 
is  necessary  ;  otherwise,  condensation  must  be 
resorted  to.  Shortly  before  the  appearance  of 
my  work,  Soxhlethad  attributed  the  well-recog- 
nized success  that  attends  the  pasteurization 
of  milk  to  the  subsequent  chilling  of  the  fluid  ; 
later,  upon  the  basis  of  the  facts  I  had  ascer- 
tained, he  introduced  the  method  of  treating 
children's  milk  which  goes  by  his  name.  This, 
as  a  matter  of  fact,  was  nothing  more  than  an 
exploitation  of  my  discoveries,  which  I  had 
freely  placed  at  the  disposition  of  every  one. 

Naegeli  observed,  as  Pasteur  had  done  before 
him,  that  milk  that  has  been  heated  does  not 
afterwards  become  acid,  but,  on  the  contrary, 
alkaline,  and  he  assumed  that  the  germ  that 
produced  acid  had  been  so  modified  by  the  heat 
that  its  ferment-nature  had  undergone  meta- 
morphosis. My  own  investigations  have  made 
the  following  point  clear,  namely,  that  the 
germs  producing  acid  are  actually  destroyed 
by  the  heat,  but  that  resistant  spores  of  other 
bacteria  are  present  along  with  them  in  the 
milk,  and  that  these  spores  resist  the  heat, 
subsequently  germinate  and  thereby  render 


134  BACTERIOLOGY. 

the  milk  alkaline  and  bitter.  The  bacterial 
species  concerned  in  this  matter,  and  which  be- 
long in  great  part  to  the  general  group  of  hay 
or  potato  bacilli,  were  later  studied  by  LofHer, 
Weigmann,  Kriiger  and  Fliigge.  Fliigge  and 
I  together  ascertained  that  some  of  these  bac- 
teria could  form  not  only  bitter  substances 
but  also  proteid-like  poisons.  Milk  usually 
becomes  bitter  because  of  the  formation  of  pep- 
tones ;  according  to  von  Freudenreich,  how- 
ever, certain  bacteria  may  form  other  bitter 
substances. 

Important  work  was  done  upon  the  lactic 
acid  fermentation  by  my  pupils,  Scholl  and 
Grotenfelt,  and  later  by  Weigmann,  Kriiger, 
Conn  and  Kaiser ;  Grotenfelt  first,  Weigmann 
later  and  more  accurately,  have  established  the 
fact  that  some  of  the  germs  which  form  lactic 
acid  in  milk  and  in  various  sugar  solutions, 
produce  a  fine,  aromatic  odor.1  I  had  already 
in  1889  maintained  before  the  German  dairy 
association  that  dairymen  ought  to  make  use 
of  pure  cultures  of  such  bacteria  to  bring 
about  the  souring  of  pasteurized  cream  in 
all  places  where  butter  is  made  out  of  sour 
cream  (as  is  the  case  universally  north  of  the 
Main  and  in  Scandinavia).  Grotenfelt  has  in- 

1  Cf.  Weigmann,  Zum  Butteraroma.  Centralbl.  f.  Bakt.,  Abth.  II., 
III.,  p.  497- 


THE   VITAL   PHENOMENA   OF   BACTERIA.       135 

troduced  into  Finland  this  method  of  souring 
cream ;  Weigmann  has  recommended  its  use 
in  Holstein  ;  and  Stein  and  Boggild  have  in- 
troduced it  into  Denmark  with  marked  success, 
so  that  butter  made  from  such  cream  has,  in 
the  last  year,  gained  everywhere  a  majority  of 
the  first  prizes.  In  Germany,  although  the 
method  in  the  first  instance  emanated  from  my 
laboratory,  very  little  advantage  has  yet  been 
taken  of  these  facts.  The  circumstance  that 
the  dairymen  themselves  do  not  push  the  mat- 
ter energetically,  but  are  waiting  for  State  in- 
itiative, is  in  part  to  blame  for  this  condition. 
It  is  most  necessary,  however,  to  awaken  the 
farmer,  with  or  without  State  aid,  as  is  proved 
by  the  whole  situation  of  the  butter  question. 
The  replacement  of  butter  by  "  artificial  but- 
ter" which,  when  real  oleomargarine,  is 
prepared  out  of  beef  fat,  has  not  solved  the 
question,  for  the  simple  reason  that  good  beef- 
fat  is  itself  dear,  and  hence  in  the  manu- 
facture of  oleomargarine,  other  fats,  often  of 
disgusting  nature  are  always  in  part  substi- 
tuted for  it.  Consequently  oleomargarine  is 
as  a  matter  of  fact  everywhere  sold  at  prices 
above  its  real  value  and  is  not  a  fair  substitute 
for  butter.  On  the  other  hand,  butter  is  often 
handled  on  small  farms  so  badly,  and  with  such 
lack  of  cleanliness,  that  we  can  certainly  under- 


136  BACTERIOLOGY. 

stand  why,  in  view  of  this  indifference  of  the 
producer,  the  consumer  often  prefers  oleomar- 
garine which,  to  say  the  least,  is  always  appe- 
tizingly  prepared. 

In  the  ripening  of  cheeses,  also,  bacteria  take 
part.1  Some  kinds  effect  the  natural  ripening, 
that  is,  the  transformation  of  the  casein  and 
the  production  of  aromatic  chemical  compounds 
which  impart  the  individual  flavor  to  different 
cheeses,  and  some  kinds  bring  about  the  vari- 
ous "  diseases "  of  cheese,  the  ripening  in 
wrong  ways  and  the  formation  of  poisons.  The 
studies  upon  cheese  bacteria  have  been  carried 
forward  especially  by  Freudenreich,  Adametz, 
and  Beyerinck.  If  we  except  the  use  of  the 
"  Edelpilz"  a  variety  of  the  green  pencil 
mould  (Penicillium),  in  ripening  Roquefort 
and  Gorgonzola  cheeses,  then  Persy n,  with  the 
aid  and  direction  of  Hueppe,  was  the  first  to 
put  what  was  known  in  the  matter  to  practical 
use  by  the  employment  of  pure  cultures  of 
bacteria  in  the  preparation  of  an  Edam  cheese 
to  which  prizes  have  been  repeatedly  awarded. 

The  rancidity  of  butter  due  to  formation  of 
fatty  acid  depends,  according  to  Duclaux  and 
Ritsert,  upon  the  oxidation  of  the  fat  by  at- 
mospheric oxygen  in  the  presence  of  light,  and 

1  See  also  on  this  point,  Babcock  and  Russell :  "  Unorganized 
Ferments  of  Milk  :  a  New  Factor  in  the  Ripening  of  Cheese." 
Centralbl.  f,  Bakt.,  Abth.  II.,  III.,  p.  615. 


THE   VITAL   PHENOMENA   OF   BACTERIA.       137 

in  part  also,  according  to  Kriiger  and  V. 
Klecki,  upon  the  production  of  acid  from  the 
milk-sugar.  The  first  sort  of  decomposition 
can  be  avoided  by  careful  exclusion  of  the 
butter  from  light  and  air,  the  latter  by  heat- 
ing or  addition  of  salt.  The  "  rancidity  "  first 
mentioned  was  formerly  confounded  with  real 
"  acidity." 

According  to  Haenlein,1  we  have  reason  to 
hope  that  the  tanning  industry  also  will  derive 
practical  benefit  from  bacteriology. 

The  steeping  of  flax-stems  in  water  as  prep- 
aration for  retting  is  performed  for  the  pur- 
pose of  bringing  about  a  process  of  bacterial 
decomposition,  and  accurate  study  of  this  pro- 
cess will  perhaps  enable  us  to  isolate  bacterial 
species  specially  fit  for  this  purpose  and  to  use 
them  in  pure  cultures. 

In  all  these  cases  in  which  pure  cultures  of 
bacteria  are  employed  for  reaching  a  desired 
specific  effect,  it  is  always  our  aim  to  obtain  a 
definite  species  of  bacterium  and  to  utilize  the 
constancy  of  this  species  to  generate  definite 
products ;  whence  we  might  infer  that  the 
constancy  with  which  a  species  produces  pig- 
ment or  fermentation  or  disease  is  absolute, 
and  that  the  effect  is  wholly  contingent  upon 
the  kind  of  bacterium  present. 

i  Centralbl.  f.  Bakt.,  Abth.  II.,  I.,  p.  26. 


BACTERIOLOGY. 


Cycles  of  Activity  and  Adaptation. 

The  fact,  however,  is  quite  otherwise.  Perty  , 
Billroth,  and  Naegeli  long  ago  denied  that  con- 
stancy of  species  existed  among  bacteria. 
Billroth  derived  all  disease-producing  bacteria 
from  a  species  named  by  him  Coccobacteria 
septica,  while  Naegeli  asserted  that  the  form 
and  action  of  bacteria  vary  without  limit. 
Buchner  was  the  first  to  succeed  in  treating 
the  anthrax  bacillus  so  that  it  lost  its  power 
to  provoke  disease  and  comported  itself  like  a. 
mere  bacillus  of  putrefaction.  It  is  true  he 
did  not  interpret  this  result  correctly,  since 
he  was  led  to  believe  that  the  anthrax  bacillus 
had  been  converted  into  the  hay  bacillus. 
Pasteur  next  observed  that  the  bacteria  of 
chicken  cholera  could  be  made  to  lose  their 
ability  to  produce  the  disease,  and  later  it  was 
ascertained  that  nearly  all  of  the  disease-pro- 
ducing germs  could  be  similarly  attenuated. 
Fitz  first  established  the  same  fact  concerning 
the  bacteria  of  the  butyric  acid  fermentation, 
and  Hueppe  concerning  the  lactic  acid  germs, 
while  Schottelius  and  Scholl  proved  the  same 
thing  concerning  the  pigment  bacteria. 

The  ability  of  bacteria  to  form  pigments, 
fermentation  products,  or  poisons,  either  in 
their  growth  upon  dead  substance  or  in  the 


THE   VITAL   PHENOMENA   OF   BACTERIA.       139 

living  organisms,  or  to  produce  disease,  is,  as 
a  matter  of  fact,  variable.  It  can  dimmish, 
but  it  can  also  under  some  conditions  increase. 

Bacteria  depend  for  their  provision  of  food 
and  energy  upon  the  conditions  of  nutrition. 
If  these  conditions  remain  constant  the  action 
of  the  bacteria  does  not  vary.  If  the  condi- 
tions of  existence  do  not  remain  constant,  one 
of  three  things  comes  to  pass.  Either  the 
bacteria  change  in  form  and  action  and  adjust 
themselves  to  the  new  conditions,  or  they  form 
spores  which  preserve  the  species  until  better 
times  return,  or  they  fail  to  adapt  themselves 
at  all  and  so  perish.  The  various  kinds  of  pig- 
ment, ferment,  and  disease-producing  bac- 
teria are  therefore  in  fact  not  to  be  considered 
as  species  in  the  natural  history  sense,  but  as 
nutritional  modifications. 

For  this  reason  we  recognize  the  existence 
of  complete  "cycles  of  activity."  According 
to  Fitz  the  butyric  acid  germ  forms  butyric  acid 
out  of  the  saccharoses  as  the  chief  product,  and 
butyl  alcohol  as  a  by-product ;  while  out  of 
glycerin  it  forms,  besides  butyric  acid,  much 
normal  butyl  alcohol,  and  as  by-products  propyl 
glycol  and  lactic  acid.  The  bacteria  of  glanders 
form  a  brown  pigment  on  potato,  and  their 
growth  is  accompanied  by  decrease  of  virulence  ; 
the  yellow  pus-coccus  (Staphylococcus  pyogenes 


140  BACTERIOLOGY. 

aureus)  forms  a  golden-yellow  pigment,  induces 
suppuration,  and  in  sugar  solutions  produces 
lactic  acid  ;  the  comma  bacillus  of  Asiatic  chol- 
era causes  disease  in  man,  forms  in  its  growth 
upon  potato  a  yellowish  brown  pigment,  and  in 
sugar  solutions  produces  Isevo-rotatory  lactic 
acid  ;  the  common  bacillus  of  the  colon  (B.  colt 
communis)  as  a  rule  lives  a  harmless  sapro- 
phytic  existence  in  the  intestine,  but  may  also 
cause  serious  illnesses  and  inflammations, 
while  in  sugar  solutions  it  can  effect  a  lactic 
acid  fermentation,  and  when  grown  on  potato 
forms  a  dirty  brown  pigment.  B.  prodigiosus 
produces  red  spots  upon  substances  rich  in 
starch,  such  as  potatoes  or  wafers,  a  phenome- 
non which  in  early  times  was  regarded  as  the 
miracle  of  the  bleeding  host ;  when  grown  at 
higher  temperatures  it  brings  about  vigorous 
lactic  acid  fermentation  without  any  produc- 
tion of  pigment.  The  mere  fact  that  it  is  pos- 
sible to  obtain  parasitic  or  zymogenic  germs 
in  pure  culture,  and  to  cultivate  them  as 
harmless  saprophytes  upon  various  lifeless 
nutrient  media  shows  that  it  is  impossible  to 
divide  bacteria  into  physiological  species  ac- 
cording to  their  mode  of  action. 

This  is  practically  opposed  to  the  ideas 
which  were  expressed  cautiously  by  Ferdinand 
Cohn  and  Schroter,  and  more  outspokenly  by 


THE   VITAL   PHENOMENA   OF   BACTERIA.       141 

R.  Koch.  According  to  the  conception  ad- 
vanced by  the  latter  it  is  the  bacillus,  always 
constant,  that  is  the  "  cause  "  of  the  typical  or 
specific  fermentation  or  disease :  it  alone  pro- 
duces the  uniformity  of  effect.  In  reality 
the  bacillus  adapts  itself  to  its  surroundings 
and  remains  the  same  so  long  as  they  remain 
the  same,  but  changes  if  they  vary.  The  con- 
stancy of  those  external  conditions  to  which  bac- 
teria must  adjust  themselves  alone  determines 
the  uniformity  of  the  effects  produced. 

The  full  significance  of  the  foregoing  facts 
may  perhaps  be  gathered  from  the  following 
considerations.  If  a  person  contracts  a  bacterial 
disease,  tuberculosis  for  example,  then,  accord- 
ing to  Koch,  only  the  tubercle  bacillus  can  be 
held  responsible.  It  is  just  this  belief  that 
has  made  the  science  of  bacteriology  so  popu- 
lar in  the  eyes  of  the  unreflecting  multitude 
and  of  many  easy-going  physicians.  We 
need  no  longer,  it  is  supposed,  be  solicitous 
about  our  own  mistakes  and  peccadilloes. 
Come  what  may,  we  are  morally  protected, 
and,  secure  in  the  consciousness  of  our  in- 
dividual merit,  we  now  lay  all  responsibility 
upon  "  the  bacteria  "  as  formerly  upon  "  catch- 
ing cold."  A  fatal  blow  is  dealt  to  these  self- 
deceptions  and  illusions  by  simply  pointing  to 
the  fact  that  bacteria  provoke  fermentation 


142  BACTERIOLOGY. 

only  when  they  come  in  contact  with  ferment- 
able substances  under  proper  conditions,  and 
produce  illness  and  disease  only  when  predis- 
position toward  disease  exists.  Such  liability 
or  predisposition  we  may  either  inherit  from 
others  or  acquire  by  faults  of  our  own.  Where 
no  susceptibility  to  disease  exists,  we  may 
harbor  the  bacillus  with  impunity.  We  should, 
then,  revile  the  malicious  bacteria  no  longer,  but 
take  ourselves  to  task  and  mend  our  own  ways. 
Not  that,  some  measure  of  reform  having  been 
effected,  we  should  behave  ourselves  irration- 
ally for  eleven  months  in  the  year,  then  go  to 
a  medical  Tetzel  and  have  prescribed  as  in- 
dulgence a  four  weeks'  sojourn  at  a  watering- 
place.  It  is  better  for  the  majority  of  men  to 
put  themselves,  through  sensible  ways  of  liv- 
ing, into  such  a  condition  that  bacteria  can  get 
no  lodgment  in  their  system.  This,  in  few 
words,  is  the  practical  lesson  of  bacteriological 
discoveries,  Koch  to  the  contrary  notwithstand- 
ing. It  is  a  less  comfortable  doctrine,  but  it  is 
scientifically  more  nearly  correct  than  the 
other. 

The  action  of  environment  upon  bacteria 
may  be  still  further  considered.  If  a  bacter- 
ium that  produces  disease  or  that  causes  fer- 
mentation or  that  forms  pigment  be  cultivated 
for  a  long  time  under  conditions  in  which  it 


THE   VITAL   PHENOMENA   OF   BACTERIA.       143 

cannot  exert  its  peculiar  activity,  it  generally 
adapts  itself  to  the  new  conditions  so  com- 
pletely that  it  entirely  unlearns  its  original 
mode  of  action.  In  our  laboratories  many 
disease  and  ferment  germs  have  become  harm- 
less saprophytes  though  long-continued  culti- 
vation in  nutrient  broth  or  gelatin.  It  is  possi- 
ble also,  if  the  attempt  be  not  too  long  delayed, 
to  accustom  these  bacteria  again  to  their  origi- 
nal mode  of  activity  by  supplying  their  original 
conditions  of  life. 

The  form  of  bacteria,  as  well  as  their  func- 
tion, changes  in  response  to  changed  condi- 
tions of  life.  The  ray-fungus  (Actinomyces) 
develops  its  characteristic  form  only  in  the 
animal  organism.  The  so-called  tubercle  bac- 
illus is  not  a  bacillus  at  all  from  the  point  of 
view  of  bacterial  classification,  but  a  parasitic 
growth-form  of  a  pleomorphic  mould.  It  is 
now  well  established  that  there  are  species  of 
bacteria  that  pass  through  only  a  small  cycle 
of  forms,  while  other  species  show  many  forms 
in  the  course  of  their  development,  a  point 
that  has  been  elucidated  chiefly  by  the  inves- 
tigations of  Zopf  and  Winogradsky.  At  one 
time  pleomorphism  was  generally  confounded 
with  the  variability  of  individual  forms  accord- 
ing to  the  substratum,  an  error  to  which  an 
end  was  put  some  years  ago  by  the  demonstra- 


144  BACTERIOLOGY. 

tion  that  pleomorphic  species  may  be  rela- 
tively constant  in  form,  and,  conversely,  that 
the  forms  of  simple  species  may  be  very  vari- 
able. Buchner,  Gruber  and  MetschnikofT 
have  discovered  important  examples  of  this 
rule. 

If  the  activities  of  bacteria  be  artificially 
modified, — if  for  instance,  pathogenic  bacteria 
be  so  attenuated  that  they  have  little .  or  no 
effect  upon  animals, — in  such  a  case  morpho- 
logical changes  in  the  germ  may  be  regarded 
as  degenerative  ;  the  species  may  not  only  be 
less  virulent,  but  also  grow  more  feebly.  It 
is  possible,  however,  to  destroy  the  power  of 
the  "  specific  "  action  upon  animal  organisms 
while  the  bacteria  themselves  remain  vigorous 
or  indeed  grow  even  more  vigorously.  In 
some  cases  of  this  sort,  disease  germs  adapt 
themselves  exclusively  to  decomposition  and 
become  mere  saprophytes.  The  ability  of 
bacteria  to  form  pigments,  fermentation- 
products  and  poisons  and  to  provoke  disease 
is  proved  by  accurate  investigation  to  be  sim- 
ply a  quality  of  adaptation,  and  a  knowledge 
of  this  fact  makes  it  possible  for  us  to  discuss 
scientifically  the  question,  involved  as  it  is  at 
every  point,  of  the  causes  of  disease  (Ch.  IV.). 
Koch's  belief  that  the  "  cause "  of  disease 
is  the  constancy  of  the  "  specific  "  disease-pro- 


THE   VITAL   PHENOMENA   OF   BACTERIA.      145 

ducing  bacteria  renounces  at  the  outset  a 
scientific  explanation.  With  the  abandon- 
ment of  Koch's  position,  which  has  been  made 
inevitable  by  the  facts  discovered  in  the  last 
ten  years,  bacteriology  has  progressed  beyond 
the  stage  of  a  natural  history  subject  and  ad- 
vanced to  a  truly  scientific  standpoint. 


CHAPTER  III. 

BRIEF    DESCRIPTIONS     OF     THE     MOST     IMPOR- 
TANT  PATHOGENIC   BACTERIA. 

THE  starting-point  of  the  discoveries  enu- 
merated in  this  chapter  was  the  observation  that 
definite  bacteria  with  well-marked  character- 
istics occur  in  certain  diseases.  For  example, 
spirally  twisted  filaments  were  observed  by 
Obermeier  in  the  disease  known  as  relapsing 
fever,  rodlets  were  found  by  Koch  in  anthrax, 
and  chain-cocci  in  erysipelas.  The  microbes 
which  have  been  brought  to  light  by  investiga- 
tion of  this  kind  belong  mostly  to  the  class  of 
bacteria.  Such  microbes  found  accompanying 
disease  have  been  discovered  successively  not 
only  in  many  epidemic  diseases,  but  also  in  so- 
called  organic  diseases  like  pneumonia,  and  in 
constitutional  diseases  like  consumption  ;  and 
they  have  been  found  so  situated  that  their 
causal  connection  with  these  diseases  is  gener- 
ally acknowledged.  Koch  claimed  that  three 
points  must  be  determined  in  order  to  afford 

proof  of  this  causal  relation  :  (i).  The  microbes 
<  146 


DESCRIPTIONS   OF   PATHOGENIC   BACTERIA.     147 

should  be  found  in  such  numbers  and  in  such 
positions  that  their  presence  could  explain  the 
characteristic  symptoms  of  the  disease ;  (2) 
They  should  be  grown  in  pure  culture  outside 
of  the  body ;  (3)  These  pure  cultures,  when 
inoculated  into  susceptible  animals,  should  in- 
duce the  same  disease.  Proof  on  each  of  these 
several  heads  could  be  furnished  in  the  case  of 
many  diseases,  for  example,  in  the  case  of 
septicaemic  diseases  like  anthrax  and  in  tuber- 
culosis. On  the  other  hand,  proofs  on  heads  (2) 
and  (3)  failed  in  relapsing  fever,  proof  (i)  was 
not  forthcoming  for  diphtheria  and  lockjaw, 
nor  were  proofs  (i)  and  (3)  for  cholera. 

It  was  necessary  then  to  make  a  further  ad- 
vance. The  fact  that  was  first  recognized, 
although  it  did  not  at  once  receive  the  attention 
it  deserved,  was  the  existence  of  a  suscepti- 
bility to  disease.  Only  if  an  animal  was  pre- 
disposed to  "  take "  the  disease  in  question 
could  the  disease  be  imparted  to  it.  If  an  ani- 
mal was  not  susceptible,  it  was  not  made  ill 
or  affected  by  the  bacteria  in  any  way.  It  was 
next  observed  that  certain  bacteria  did  not 
produce  their  deleterious  effect  mechanically 
by  their  presence  and  increase  in  the  organs, 
but  rather  chemically  through  the  formation 
of  poisons.  (It  is  certainly  remarkable  that 
Koch  who  had  made  the  first  of  these  observa- 


OF  THE 

tJNIVERSITY 


148  BACTERIOLOGY. 

tions  in  1878  could  yet  in  1880  confidently 
advance  his  three  requirements).  The  fact 
soon  became  manifest  also  that  not  all  those 
bacteria  which  the  microscope  showed  to  be 
associated  with  certain  diseases  could  be  culti- 
vated outside  of  the  body  ;  in  such  cases  it 
was  not  possible  to  obtain  pure  cultures  and 
infect  animals  with  them.  It  became  evident 
further  that  the  bacterial  forms  themselves 
were  not  always  distinct,  typical  and  specific, 
and  that  the  simple  form-characteristics  relied 
on  in  earlier  times  could  not  be  made  use  of, 
but  recourse  must  be  had  to  other  differential 
diagnostic  characters.  Many  bacteria  also 
were  found  to  be  commonly  harmless,  although 
able  to  cause  disease  under  special  conditions. 
In  the  light  of  these  discoveries,  all  our 
classifications  of  bacteria  are  seen  to  be  beset 
with  insuperable  difficulties.  If  we  classify 
according  to  bacterial  genera,  the  germs  of 
disease  are  widely  separated  from  one  another ; 
if  we  classify  according  to  diseases,  the  bac- 
terial groups  are  broken  up.  Often  one  does 
not  know,  in  a  given  disease,  whether  to  attach 
more  importance  to  the  localization  of  the 
germs  in  single  organs  or  tissues  or  to  the 
general  effect.  The  grounds  for  many  of 
these  perplexities  will  be  explained 'later  very 
simply  when  I  take  up  scientifically  the  dis- 


DESCRIPTIONS   OF   PATHOGENIC   BACTERIA.     149 

cussion  of  etiology.  For  the  present,  a  pre- 
liminary survey  is  sufficient. 

A  primary  distinction  is  often  made  between 
the  truly  infectious  organisms,  organisms 
namely  which,  when  introduced  in  small  num- 
bers into  the  body  of  men  or  the  lower  ani- 
mals, can  increase  there  abundantly ;  the  poison- 
ous or  toxic  bacteria  which,  when  introduced 
even  in  small  numbers  into  the  body  of  the  host, 
produce  poison  ;  and  the  phenomenon  of  in- 
toxication or  poisoning  which  is  caused  only 
by  the  direct  incorporation  of  quantities  of  toxin. 
Virulence  may  be  said  in  general  to  be  the 
power  to  grow  or  produce  poisons  in  the  body. 

Some  bacteria  produce  ill  effects  by  poisons 
which  they  generate  outside  of  the  body  dur- 
ing the  course  of  the  decomposition  of  dead 
organic  material,  the  organisms  themselves  not 
being  able  to  grow  in  the  animal  body.  A. 
group  of  facts  bearing  on  this  point  was  first 
securely  established  by  Panum  I  in  1874.  To 
this  class  belong  many  of  the  bacteria  of  putre- 
faction. In  some  instances  after  the  body  has 
been  weakened  by  the  poisons,  these  putre- 
factive bacteria  may  become  able  to  multiply 
within  the  organism. 

B.  Proteus,  discovered  by  Hauser2  in  1885, 

1  Virchow's  Archiv,  LX.,  p.  358. 

2  Ueber  Faulnissbakterien,  1885. 


150  BACTERIOLOGY. 

was  probably  included  at  first  in  the  collective 
species  "  B.  termo"  It  forms  spherical  cells 
and  rodlets  which  unite  in  long  filaments,  and 
belongs,  therefore,  among  the  arthrobacteria. 
Its  vegetative  rod-forms  have  numerous  diffuse 
flagella ;  it  liquefies  gelatin,  producing  at  the 
same  time  a  carrion-like  odor  ;  it  does  not  stain 
by  Gram's  method.  If  the  organism  is  in- 
jected into  the  vein  of  a  dog,  the  animal  sickens 
with  vomit  and  diarrhoea  both  accompanied  by 
haemorrhage  and  with  yellow  discoloration  of 
the  sclera.  The  same  hsemorrhagic  enteritis 
occurs  when  filtered  cultures  are  injected,  hence 
the  inference  that  we  have  here  a  case  of  simple 
intoxication.  In  man,  Proteus  is  sometimes 
found  in  purulent  and  malodorous  phlegmon- 
ous  inflammations,  in  the  so-called  putrid  in- 
toxications, in  acute  jaundice  (Weyl's  disease) 
where  it  occurs  in  the  urine,  and  in  some  cases 
of  rag-pickers'  disease. 

B.  pyocyaneus*  discovered  by  Gessard,  is 
known  both  in  the  rod  form  and  in  the  fila- 
mentous form  and  is  also  to  be  regarded  as  an 
arthrpbacterium.  It  is  characterized  by  the 
blue-green,  sometimes  leek-green  color,  that  is 
developed  in  cultures  (cf.  pyocyanin  p.  122). 
In  rabbits  it  usually  produces  only  a  general 

1  Cf.  Barker,  Journ.  of  the  Amer.   Med.  Assoc.,  XXIX.,  No.  5,  p. 
213. 


DESCRIPTIONS   OF   PATHOGENIC   BACTERIA.     151 

poisoning  ;  at  times,  however,  it  is  very  virulent 
and  multiplies  in  the  organism  so  that  a  true 
infection  exists.  It  has  been  found  in  cases 
of  general  hsemorrhagic  sepsis  and  severe 
diarrhoea  in  children  ;  in  such  cases  however 
the  toxic  action  appears  to  be  more  conspicu- 
ous than  the  effects  due  to  multiplication  of 
the  organism.  Occasionally,  it  is  found  also 
in  the  inflammation  of  serous  membranes, 
while  upon  wounds  it  attracts  attention  more 
by  the  discoloration  of  the  bandages  which  it 
produces  than  by  its  growth. 

In  the  case  of  these  two  putrefactive  bacteria 
the  distinction  between  intoxication,  real  toxic 
action,  and  real  infection  is  not  sharply  marked. 
Only  in  regard  to  their  occurrence  in  human 
beings  need  this  distinction  be  taken  into  con- 
sideration ;  there  they  produce  their  effect 
chiefly  through  intoxication.  In  this  connec- 
tion it  may  be  mentioned  in  passing  that  bac- 
teria which  are  wholly  without  effect  upon  man 
and  the  higher  animals,  and  which  are  for  them 
neither  infectious  nor  toxic,  may  yet  be  infec- 
tious for  lower  organisms,  such  as  insects.  An 
instance  of  this  is  the  infection  of  flies  by  the 
hay  bacillus. 

Bacteria,  which  are  neither  toxic  nor 
infectious  may  yet  prove  fatal  to  warm- 
blooded animals  when  injected  in  very  great 


I$2  BACTERIOLOGY. 

numbers.  In  very  large  quantities  bacterial 
protoplasm  or  bacterial  proteid  is,  like  any 
heterogeneous  foreign  proteid,  poisonous  to 
animals,  as  Hueppe  has  proved  experi- 
mentally to  be  the  case  with  a  whole  series 
of  harmless  bacteria  and  various  kinds  of 
proteids.  Landois,  Daremberg  and  Buchner 
discovered  earlier  that  the  blood-serum  of  one 
species  of  animal  destroys  the  blood-corpuscles 
of  another.  For  a  similar  reason,  probably, 
dead  cultures  of  B.  prodigiosus  or  of  the  hay 
bacillus  kill  animals  just  as  surely  as  dead 
cultures  of  pathogenic  bacteria,  and  indeed  just 
as  surely  as  living  infectious  and  toxic  bac- 
teria. In  the  conduct  of  experiments,  there- 
fore, it  is  necessary  to  consider  not  only  the 
poison  contained  in  the  poisonous  culture 
fluid,  which  is  able  to  produce  its  effect  after 
the  bacteria  have  been  removed  by  filtration, 
but  also  the  quantity  of  bacterial  protoplasm 
introduced  into  the  body  of  an  animal.  The 
transitions  from  infection  to  intoxication,  from 
disease  to  poisoning,  are  therefore  manifold 
and  various  ;  and  as  a  matter  of  fact  these 
phenomena  usually  occur  side  by  side. 

A  small  number  of  bacteria  is  sufficient  for 
infection.  In  many  cases,  experimentally 
well  established,  a  single  germ  is  able  to  pro- 
voke a  disease.  This  is  true  as  regards  the 


DESCRIPTIONS   OF   PATHOGENIC   BACTERIA.     153 

infection  of  white  mice  with  anthrax  and  young 
rabbits  with  chicken  cholera.  The  bacteria 
multiply  and  overgrow  the  organs,  generating 
during  their  growth  poisons  or  toxins  which 
cause  the  illness  of  the  host,  and,  hand  in 
hand  with  this  multiplication,  the  older  germi 
die  off  and  also  act  injuriously  for  the  reason 
that  they  are  so  much  foreign  protoplasm. 
In  the  course  of  multiplication  the  bacteria 
attack  the  proteid  of  the  body  and  split  off 
from  it  poisons,  a  process  which  can  take  place 
outside  as  well  as  inside  the  bacterial  cells. 
This  chemical  action  is  at  first  a  pure  split- 
ting, an  anaerobic  process.  The  bacteria  are 
also  able  to  consume  the  oxygen  in  the  blood 
or  tissue  juices,  and,  in  return,  generate  car- 
bonic acid,  so  that  an  overloading  of  the  blood 
with  carbonic  acid  results  in  a  development 
of  heat,  the  latter  phenomenon  expressing 
itself  in  a  rise  of  temperature,  that  is,  in  fever 
(C.  Roser).  But  the  poisons  produced  by  the 
bacteria  are  also  able  to  stimulate  the  heat- 
regulating  centres  and  so  act  in  a  more  typi- 
cal manner  upon  the  temperature.  Generally 
all  these  processes  or  several  of  them  at  least 
concur  in  bringing  about  the  final  result, 
namely,  the  process  and  symptoms  of  disease  ; 
and  for  this  reason  we  witness  individual  de- 
partures from  the  traditional  disease-schema. 


1 54  BACTERIOLOGY. 

The  "  specific  "  action  of  bacteria  must  there- 
fore not  be  represented  too  simply  and  schem- 
atically. There  is  always  involved  the  ques- 
tion of  a  reciprocal  action,  a  struggle  of  the 
complicated  bacterial  cells  with  the  compli- 
cated body-cells. 

In  general,  we  understand  by  the  "  specific  " 
poisonous  action  of  bacteria,  the  action  of  the 
poisons  or  toxins  split  off  from  proteids  inside 
or  outside  the  bacterial  cell.  The  bacterial 
protoplasm  is  able,  not  only  to  form  such 
"  specific  "  poisons  by  the  demolition  of  pro- 
teid  compounds,  but  also  to  build  them  up  out 
of  simple  substances  such  as  ammonium  lactate 
and  asparagin.  (Hueppe  has  shown  that  this 
is  .true  also  for  the  pigment  bacteria).  The 
action  of  these  poisons  is  therefore  not  the 
same  as  the  general  action  of  bacterial  proto- 
plasm, for  the  effect  of  the  latter  is  due  to  its 
being  foreign  proteid.  In  the  latter  connec- 
tion it  has  been  shown  that  the  poisonous 
effect  of  foreign  proteids,  even  when  it  is  ex- 
erted by  bacteria,  always  consists  in  a  lowering 
of  the  body  temperature,  while  the  "  specific  " 
poisonous  effect  consists  sometimes  in  a  height- 
ening sometimes  in  a  lowering  of  temperature, 
and  in  other  cases  expresses  itself  in  other 
and  various  symptoms,  such  as  paralysis,  con- 
vulsions or  necrosis,  compared  to  which  the 


DESCRIPTIONS   OF   PATHOGENIC   BACTERIA.    155 

influence  upon  temperature  is  of  secondary 
importance. 

Some  ten  or  twelve  years  ago  it  was  perfectly 
easy  to  describe  and  define  disease-producing 
bacteria.  In  the  state  of  our  knowledge  at 
that  time  it  could  be  said,  for  example,  that 
anthrax  bacilli  are  microbes  which  always 
occur  in  typical  situations  in  the  organism  af- 
fected by  anthrax,  and  which  on  being  trans- 
ferred to  another  organism  can  again  cause 
anthrax.  To-day  we  know  that  only  the  first 
of  these  statements  is  even  approximately  cor- 
rect. As  regards  the  transfer  to  another  or- 
ganism, one  might  almost  as  well  say  that  an- 
thrax bacteria  do  not  cause  anthrax,  a  paradox 
which  may  be  explained  very  simply.  The 
virulence  of  the  bacteria  fluctuates  greatly  and 
it  is  this  fact  that  renders  dubious  the  issue  of 
many  inoculation  experiments.  I  shall  dis- 
cuss these  questions  later,  but  it  seems  advisr 
able  to  mention  them  now  in  order  to  emphasize 
the  scientific  inadequacy  of  the  conventional 
schematic  representations  according  to  which 
specific  bacteria  are  regarded  as  the  "  cause  " 
of  specific  diseases. 

In  direct  relation  to  the  intoxications  pro- 
duced by  poisons  formed  outside  of  the  body 
and  introduced  into  it,  stand  the  septicaemia, 
pysemic,  phlegmonous  and  erysipelatous  pro- 


156  BACTERIOLOGY. 

cesses.  If  animals  are  injected  intravenously, 
snbcutaneonsly,  or  intraperitoneally  with 
putrid  fluids  they  die,  but  not  always  in  con- 
s.quence  of  the  poison  introduced,  for  some- 
times, especially  at  the  beginning  of  the  pro- 
cess of  putrefaction,  bacteria  occur  which  are 
able  to  multiply  in  the  body  of  the  animal  ex- 
perimented upon.  If  this  increase  takes  place 
in  the  blood  it  is  called  septicaemia  ;  the  visi- 
ble changes  do  not  go  beyond  bleeding  or 
haemorrhage.  If,  however,  several  metastatic 
localizations  in  the  form  of  suppurations  out- 
side of  the  blood-vessels  supervene,  we  speak 
of  the  affection  as  pyaemia.  If  the  growth 
occurs  in  the  skin  we  call  it  erysipelas,  if  sub- 
cutaneously,  phlegmon.  A  sharp  line  of  de- 
marcation between  these  processes  does  not, 
however,  exist  and  the  same  bacterial  species 
evokes  sometimes  one,  sometimes  another 
process. 

Anthrax  (Fig.  24).  The  anthrax  bacilli 
were  first  observed  by  Pollender  in  1849,  an(^ 
by  Davaine  and  Rayer  in  1850,  and  were 
accurately  studied  by  Davaine  and  more 
especially  by  Koch/  who  discovered  also  the 
spore-formation.  The  anthrax  bacilli  are  non- 
motile  rods  of  10-1.5."  in  breadth,  and  about 
in  length ;  both  the  size  and  the  shape 

1  Cohn,  Beitragez.  Biol.  d.  Pflanz.,  II.,  1876. 


1. 


Fig.  24. — Anthrax  bacteria. 

1.  From  spleen  pulp,  (i.  1200). 

2.  From  the  blood,  showing  possession  of  capsule,  (1:1000). 

3.  Edge  of  a  culture  showing  filamentous  windings  of  the 
so-called  spirulina  type,  11:300). 

4.  Spore  formation,  (I  •  500). 


DESCRIPTIONS   OF   PATHOGENIC   BACTERIA.    157 

of  the  rods  vary  with  the  conditions  of  nutri- 
tion. In  the  blood  they  occur  isolated  or  in 
short  threads  ;  in  culture  fluids  outside  of  the 
body,  however,  they  proliferate  into  long  mat- 
ted filaments.  Attenuated  anthrax  bacilli  can 
also  form  long  threads  in  the  blood  which  re- 
semble those  of  the  bacillus  of  malignant 
oedema.  The  anthrax  bacillus  stains  by 
Gram's  method.  In  cultures  it  is  not  exact- 
ing ;  it  thrives  in  gelatin,  agar,  and  bouillon, 
and  upon  potato,  and  forms  characteristic  col- 
onies of  tangled  threads.  In  bouillon  it  forms 
below  the  surface  festoons  of  intertwined  fila- 
ments. It  grows  between  i2°-42°  C,  and 
thrives  best  at  blood  temperature  ;  above  42°, 
its  growth  is  perceptibly  interfered  with.  En- 
dospores.are  formed  between  18°  and  42°,  but 
with  the  higher  temperatures  they  are  formed 
more  quickly  and  abundantly.  The  organism 
is  a  typical  bacillus.  Free  oxygen  is  neces- 
sary for  spore-formation,  hence  this  process  can 
occur  only  outside  of  the  animal  body.  Certain 
methods  of  staining  show  that  in  the  blood  the 
individual  rods  are  usually  not  rounded  at  the 
ends,  but  are  square-cornered  or  even  swollen 
like  joints  of  bamboo,  while  unstained  rods 
from  fresh  cultures,  and  often  also  those  from 
blood  appear  rounded ;  in  the  blood  also  cap- 
sules around  the  bacilli  are  often  plainly  visible. 


158  BACTERIOLOGY. 

Cattle,  the  European  races  of  sheep,  goats, 
and  horses  as  well  as  deer  and  roe  are  very 
susceptible  to  anthrax;  the  Algerian  sheep 
resist  infection.  Dogs  develop  a  generalized 
infection  only  after  intravenous  injection;  with 
subcutaneous  injection,  abscesses  arise  ;  young 
white  rats  are  susceptible,  older  rats  as  a  rule 
develop  only  local  abscesses,  but  septicaemia 
may  be  produced  by  the  injection  of  very  large 
numbers  of  bacilli.  Common  frogs  and  tree- 
toads  are  refractory  toward  anthrax  at  room- 
temperature,  but  succumb  if  the  temperature 
be  raised ;  the  tree-toads  are  the  more  resist- 
ant. Toads  succumb  at  the  room-tempera- 
ture. Domestic  fowls  are  resistant  to  anthrax, 
but  can  be  made  susceptible  by  chilling, 
and  pigeons  may  be  made  susceptible  by 
hunger. 

Man  is  only  relatively  susceptible  to  the 
disease  and  a  local  disturbance  in  the  form  of 
a  carbuncle  always  arises  at  the  place  of  inocu- 
lation ;  when  this  is  in  the  skin  it  takes  the 
form  of  a  "  malignant  pustule  "  ;  in  the  intes- 
tine, that  of  an  "  intestinal  mycosis."  The 
carbuncle  may  heal,  or  a  generalized  infection 
or  septicaemia  may  spread  out  from  it. 

Infection  of  the  lungs  with  anthrax  occurs 
in  people  who  are  engaged  in  the  plucking 
and  sorting  of  wool.  This  form  of  anthrax  is 


DESCRIPTIONS   OF   PATHOGENIC    BACTERIA.    159 

called  wool-sorters'  or  rag-pickers'  disease.1 
Infection  of  the  skin  may  result  from  the  bite 
of  insects  which  have  fed  upon  animals  sick 
with  anthrax  and  ingested  the  rods  with  the 
blood,  or  from  the  handling  of  hides  to  which 
spores  cling.  Anthrax  of  the  lungs  and  in- 
testine in  the  human  subject  is  always  to  be 
referred  to  spore  infection. 

Buchner  showed  experimentally  that  the 
inhalation  of  spores  led  to  a  general  anthrax 
infection  without  localization  in  the  lungs, 
while  inhalation  of  the  bacilli  produced  an 
inflammation  of  the  lungs.  Cutaneous  an- 
thrax, which  is  strictly  contagious,  appears 
only  sporadically,  or  is  encountered  only  in 
individual  cases  during  an  epidemic.  Spore 
infection  in  animals  is  always  dependent  upon 
the  external  conditions,  for  spores  are  formed 
only  in  those  places  in  a  pasture-ground  which 
have  been  frequented  by  diseased  animals,  or 
where  the  dead  bodies  of  infected  animals  have 
been  interred.  Stable  epidemics  are  usually 
traced  to  the  hay  gathered  from  such  localities. 

What  is  sometimes  regarded  as  the  inherit- 
ance of  the  disease  may  be  simply  intra-uterine 
infection.  A  healthy  placenta  is  not  traversed 
by  bacilli,  but  passage  may  occur  if  the  blood- 

1  In  some  cases  of  "  rag-pickers'  disease,"   however,  not  the  an- 
thrax bacillus  but  Proteus  is  concerned. 


l6o  BACTERIOLOGY. 

vessels  have  been  injured,  as  for  instance  by 
haemorrhages.  The  placental  tissue  of  rabbits 
has  a  greater  tendency  to  haemorrhage  during 
anthrax  than  that  of  sheep,  so  that  an  intra- 
uterine  infection  results  frequently  in  the  for- 
mer animals,  Very  rarely  in  the  latter.  Such 
haemorrhages  may  occasionally  arise  through 
rupture  of  capillaries  which  have  become 
choked  with  bacilli  and  hence  be  due  to  a  me- 
chanical cause,  but  as  a  rule  they  are  to  be 
referred  to  the  effect  of  the  toxin.  Hankin, 
Brieger  and  C.  Frankel  have  prepared  from 
cultures  a  poisonous  albumose,  but  Marmier ' 
has  lately  disputed  the  proteid  nature  of  the 
poison. 

In  the  carbuncle  that  is  found  in  cutaneous 
anthrax  in  the  human  subject  there  generally 
occurs  a  mixed  infection.  This  may  lead  sec- 
ondarily to  other  septicaemias  or  to  pyaemia, 
and  in  this  way  it  happens  that  people  who  are 
healed  of  the  primary  anthrax  infection  some- 
times die  notwithstanding. 

Swine  erysipelas  and  mouse  septiccemia. 
The  bacteria  found  in  these  diseases  are  extra- 
ordinarily slender  rods  .1— ,2/*  thick  and  .8— i.o/-* 
long.  Endospore  formation  has  not  been  pos- 
itively observed,  and  whether  or  not  the  orga- 
nism is  a  true  bacillus  is  therefore  still  uncer- 

1  Ann.  de  1'Inst.  Pasteur,  IX.,  p.  533. 


ft  *• 

<% 
»  -* 

B 

f 


*s 


. 

D 


Fig.  25. — Bacteria  enclosed  in  cells.  In  consequence  of  the 
method  of  preparation  the  cell-nuclei  are  somewhat  altered. 
Bacteria  stained  red,  body  of  cell  blue. 

A,  Gonococci  from  pus,  (i:  1000). 

B,  Swine  erysipelas  (1:800);  a,  blood  corpuscle  containing 
rods;   b,  apparently  free  colony  of  rods,  which,  however, 
really  occupies  the  site  of  a  disintegrated  corpuscle. 

C,  So-called  lepra  cell.    The  cell  is  almost  completely 
rilled  with  bacteria,  so  that  the  nucleus  cannot   be   made 
out,  and  the  appearance  seems  to  be  that  of  free  colonies  of 
bacteria,  (i:  1000).     By  the  side  of  this  are  some  free  rods 
which  in  consequence  of  plasmolysis  have  the  coccothrix 
form. 

D,  Intestinal  epithelium  with  cholera  bacteria  (after  van 
Ermenghem),  1:700. 

£t  .Tubercle  bacteria  in  a  pus  cell  in  sputum,  (1:1000). 


DESCRIPTIONS   OF   PATHOGENIC   BACTERIA.    l6l 

tain.  In  gelatin  tube  culture  the  growth  along 
the  line  of  inoculation  takes  the  form  of  a 
brush,  while  single  colonies  appear  almost  like 
bone  cells  ;  the  bacteria  do  not  grow  upon 
potato,  and  upon  agar  they  do  not  grow  so 
characteristically  as  in  gelatin.  They  retain 
the  stain  when  treated  by  Gram's  method.  In 
swine  they  evoke  a  simple  cutaneous  erysip- 
elas which  makes  its  appearance  in  the  form 
of  large  patches  ;  they  may  pass  over  second- 
arily into  the  blood,  in  the  cells  of  which  they 
are  frequently  enclosed  (Fig.  256),  although 
they  occur  also  in  the  free  condition.  Rabbits 
in  like  manner  develop  erysipelas  at  the  place 
of  infection  and  from  that  starting-point  sub- 
sequently develop  septicaemia.  House  mice 
and  especially  white  mice  are  extremely  sus- 
ceptible, and  sicken  at  the  outset  with  septi- 
caemia. The  mouse  is  found  after  death  sitting 
in  a  characteristic  position  with  its  back  curved. 
Blooded  swine  are  more  susceptible  than  ordi- 
nary swine,  while  cattle,  sheep,  horses,  car- 
nivorous animals,  guinea-pigs  and  especially 
field  and  wood  mice  are  completely  resistant. 
Virulent  cultures  become  less  virulent  in  their 
passage  through  rabbits,  more  virulent  in  their 
passage  through  pigeons.  Natural  infection 
of  swine  may*  take  place  by  means  of  the  food ; 
the  bacilli  pass  out  of  the  body  with  the  excre- 


l62  BACTERIOLOGY. 

ment.  In  putrefying  fluids  the  bacilli  gener- 
ally lose  their  virulence  in  consequence  of  the 
competition  of  other  microbes.  Out  of  such 
putrid  fluids  Koch  isolated  the  bacterium  in  1 878 
and  regarded  it  as  the  germ  producing  mouse 
septicaemia,  while  Loffler  in  1882  obtained  cul- 
tures from  swine. 

Hcemorrhagic  scpticcemia.  I  have  grouped 
under  this  name  diseases  caused  by  germs 
which,  at  their  first  discovery,  were  regarded 
as  distinct  species.  Here  belong  the  germs 
causing  septicaemia  in  rabbits  (Koch),  which 
bear  the  same  relation  to  the  germs  found  in 
the  larger  domestic  animals  as  do  the  germs  of 
mouse  septicaemia  to  those  of  swine  erysipelas. 
Here  also  are  to  be  placed  chicken  cholera  (Per- 
roncito  and  Pasteur),  the  Wildseuche  and  Rin- 
derseuche  of  Bollinger,  Kitt  and  Hueppe,  and 
the  German  Schweineseuche  described  by 
Loffler. 

The  germs  occur  in  the  form  of  spheroids 
and  of  both  short  and  long  rods,  in  which  polar 
granules  usually  arise  by  plasmolysis  during 
the  process  of  staining ;  they  are  arthrosporous 
bacteria,  are  non-motile,  and  are  decolorized  by 
Gram's  method.  The  growth  in  gelatin  and 
upon  agar  and  potato  is  not  very  characteristic. 
In  peptone  solutions  the  bacteria  form  phenol 
and  indol.  Inoculated  into  the  larger  animals, 


DESCRIPTIONS   OF   PATHOGENIC   BACTERIA.    163 

the  bacteria  produce  phlegmonous  erysipela- 
tous  processes  in  the  skin  and  pneumonitic 
processes  in  the  lungs,  but  in  the  intestine 
marked  changes  are  very  seldom  brought 
about.  Spreading  from  the  place  of  inocula- 
tion a  general  infection  in  the  form  of  septicae- 
mia results.  If  fowls  are  fed  with  pure  cul- 
tures an  enteritis  is  set  up,  and  if  the  animals 
be  injected  intramuscularly  a  coagulation 
necrosis  of  the  muscular  tissue  is  caused  ;  a 
general  infection  often  concludes  both  pro- 
cesses. In  slightly  susceptible  animals  only 
local  abscesses  and  necroses  occur.  If  the 
bacillus  is  in  a  condition  adapted  for  growth 
in  the  body  of  mammals  it  is  relatively  more 
virulent  towards  them  than  towards  fowls  ;  if 
it  is  adapted  for  an  existence  in  birds  the  re- 
verse is  true.  Because  of  the  discovery  of 
these  two  extremes  it  has  been  thought  that 
two  varieties  exist,  mammalian  septicaemia 
and  avian  septicaemia,  which  however,  pass 
over  into  one  another.  Such  fluctuations  in 
virulence  in  a  state  of  nature  have  given  rise 
to  variations  in  the  statements  of  authors  re- 
garding these  diseases.'  The  fact  that  epi- 
demics are  more  often  observed  among  swine 
than  among  cattle  is  due  to  the  differences  in 
stabling  and  feeding,  swine  being  more  exposed 
to  danger,  than  the  latter.  Where  wild  swine 


164  BACTERIOLOGY. 

are  in  the  open  along  with  other  wild  animals, 
all  the  susceptible  species  sicken.  (These  epi- 
demics of  wild  animals  were  all  at  one  time  re- 
garded as  anthrax).  The  disease  may  be  con- 
tracted by  cattle,  domestic  swine,  wild  swine, 
horses,  deer,  fallow  deer,  red  deer,  rabbits,  and 
guinea-pigs, — to  which  the  foregoing  statement 
concerning  virulence  is  especially  applicable, — 
and  by  mice  ;  also  by  fowls,  pigeons,  and  geese. 
What  has  been  stated  concerning  the  virulence 
of  the  disease  for  mammals  holds  good  of  birds 
as  well.  This  disease  is  also  closely  related 
to  the  Buffelseucke  of  Italy,  the  germ  of  which, 
however,  although  forming  iiidol,  does  not  form 
phenol. 

Of  a  different  species,  though  similar  both 
in  form  and  culture,  is  the  germ  causing 
Schweinepest,  first  correctly  identified  b}^Selan- 
der.  These  bacteria  are  actively  motile  and, 
according  to  investigations  by  Hueppe,  Caneva 
and  Bunzl-Federn,  they  gelatinize  milk  with 
formation  of  alkali.  The  bacteria  of  haemor- 
rhagic  septicaemia,  on  the  other  hand,  coagulate 
milk  with  production  of  acid,  so  that  by  this 
test  a  simple  and  sure  differential  diagnosis  is 
possible.  The  American  swine  disease  or  hog 
cholera  (Salmon)  and  the  swine  plague  (Bil- 
lings) are  identical  with  this  disease.1  Whether 

1  Some   confusion  exists  here.     See  "  Additional  Investigations 


DESCRIPTIONS   OF   PATHOGENIC   BACTERIA.     165 

the  German  Schweineseuche  also  exists  in 
America  is  still  somewhat  doubtful ;  in  Ger- 
many the  Scandinavian-American  swine-plague 
has  been  observed,  at  least  sporadically.  The 
disease  manifests  itself  especially  as  a  severe 
affection  of  the  intestine. 

A  third  and  related  group  of  germs  dis- 
covered by  Reitsch  and  Joubert,  are  morpho- 
logically similar,  but  the  bacteria  are  actively 
motile,  coagulate  milk  with  production  of  acid, 
and  form  both  indol  and  phenol  in  peptone 
solutions.  The  disease  they  cause  was  ob- 
served in  Southern  France  among  swine  in- 
troduced from  Algeria.  Eberth  found  similar 
organisms  in  cases  of  ferret  disease  and  spon- 
taneous rabbit  septicaemia.  The  difference 
between  this  and  the  first  group  lies  in  the 
motility  of  the  bacteria,  and  in  the  fact  that 
the  swine  suffer  more  from  enteritis,  as  in  the 
Schweinepest. 

Two  years  ago  a  disease  of  swine  was  rife  in 
North  Germany,  the  chief  symptom  of  which 
was  a  diphtheritic  affection  of  the  large  intes- 
tine. According  to  Deupser,  motile  bacteria 
were  always  present.  Unfortunately  the  ex- 

concerning  Infective  Svvirie  Diseases  "  by  Theobald  Smith  and  V.  A. 
Moore,  U.  S.  Dept.  of  Agriculture,.  Bureau  of  Animal  Industry, 
Bull.  No.  6.  Selander  appears  to  have  worked  with  the  bacillus  of 
swine-plague  and  not  that  of  hog-cholera.  See  for  a  very  recent  dis- 
cussion of  the  nomenclature  and  etiology  of  these  diseases,  Preiss, 
Zeitschr.  f.  Thiermedicin  N.  F.  II.,  1898,  p.  i.  E.  O.  J. 


1 66  BACTERIOLOGY. 

tremely  simple  differential  diagnosis  between 
the  Schweinepest  and  the  French-Algerian 
Schweineseuche  was  not  made. 

These  various  affections  of  swine  illustrate 
in  a  striking  manner  the  importance  of  bac- 
teriology as  a  means  of  diagnosis  of  disease. 
The  German  Schweineseuche  probably  has  its 
true  home  in  the  Alps  so  that  its  epidemic  ex- 
tension in  the  year  1895  to  Hungary  and 
Servia  is  not  remarkable,  since  sporadic  cases 
have  occurred  there  for  years,  although  prob- 
ably confounded  previously  with  anthrax  or 
with  swine-erysipelas.  The  first  case  in  Bo- 
hemia was  observed  by  Hueppe  in  the  summer 
of  1895. 

The  Pyogenic  Bacteria  are,  strictly  speak- 
ing, the  staphy locoed^  which  received  this  name 
from  Ogston  because  the  cocci  in  the  tissues 
are  often  disposed  in  grapelike  clusters.  In 
cultures  they  appear  as  micrococci  which  form 
yellow,  orange  or  white  pigment  and  are  con- 
sequently distinguished  as  Staphylococcus  pyo- 
genes  aureus,  citreus  or  albtis,  respectively. 
They  liquefy  gelatin  and  coagulate  milk  ;  they 
stain  by  Gram's  method.  Introduced  subcu- 
taneously  into  the  body  of  animals  in  small 
tubes  they  exert  a  positively  chemotropic  effect 
upon  the  white  blood-corpuscles,  i.e.,  they 
attract  them.  Inoculated  directly  into  ani- 


DESCRIPTIONS    OF   PATHOGENIC   BACTERIA.     1 67 

mals  they  produce,  according  to  their  vir- 
ulence, local  suppuration,  pyaemia  or  septi- 
caemia. In  man  they  have  been  observed  in 
abscesses  and  in  inflammation  of  the  bone- 
marrow.  The  ability  to  induce  suppuration  is, 
however,  by  no  means  limited  to  these  microbes. 
If  cells  of  the  body  are  destroyed  mechani- 
cally, or  by  poisons,  the  necrotic  tissue  thus 
formed  attracts  the  white  blood-corpuscles. 
These  corpuscles  are  adapted  to  the  task  of  keep- 
ing free  the  circulatory  channels  and  at  the 
same  time  they  assist  in  the  utilization  of  the 
material  fitted  for  resorption  into  the  body. 
Hence  the  wandering-out  of  the  white  blood- 
corpuscles  from  the  blood-vessels  into  the  tis- 
sues seems  to  be  an  important  act  of  nutrition. 
When,  however,  white  blood  corpuscles  which 
have  been  thus  attracted  come  into  the  region 
of  bacterial  poisons  they  are  paralyzed  by  the 
poisons,  prevented  from  wandering  back,  and 
become  local  pus-corpuscles.  It  is  now  known, 
that,  besides  the  pyogenic  bacteria,  other  bac- 
teria also  can  bring  about  pus  formation,  and 
the  same  thing  is  true  as  well  of  bacterial 
poisons  and  of  other  poisons  such  as  corrosive 
sublimate. 

In  cases  of  severe  suppuration  the  so-called 
Streptococcus  pyogenes  or  erysipelatos  is  the  one 
most  commonly  found.  It  is  a  coccus  form 


168  BACTERIOLOGY. 

arranged  in  chains ;  and  stains  by  Gram's 
method.  According  to  its  virulence  the  Strep- 
tococcus  produces  simple  or  bullate  erysipelas 
of  the  skin,  suppuration  of  various  organs,  and 
also  acute  lung  inflammations,  of  an  erysipe- 
latous  and  spreading  character,  and  acute 
puerperal  fever.  The  same  Streptococcus  pro- 
duces also  acute  anginas  with  diphtheritic  in- 
crustations, and  the  diphtheria-like  affection 
which  attacks  a  patient  recovering  from  scarlet 
fever.  The  streptococci  found  in  the  so-called 
frambcesia,  a  skin  disease  of  the  tropics,  are 
certainly  not  the  cause  of  the  disease,  and  are 
probably  only  erysipelas  cocci  that  have  pene- 
trated the  skin  at  the  injured  places. 

In  association  with  the  process  of  caries  or 
decay  of  the  teeth  are  found  all  possible  kinds 
of  pyogenic  germs.  According  to  Miller  the 
enamel  of  the  teeth  is  first  attacked  by  acids 
which  are  formed  in  the  mouth  as  the  result  of 
bacterial  decompositions  and  then  the  pyogenic 
bacteria  in  the  mouth  penetrate  into  the  decalci- 
fied organic  substance  of  the  tooth.  If  cavities 
are  created  in  this  way  then  it  is  possible 
that  other  microbes,  as  for  example  those  of 
tuberculosis  and  actinomycosis,  may  enter  the 
body  by  way  of  the  decayed  teeth. 

If  we  consider  the  great  fluctuations  in  vir- 
ulence shown  by  the  pyogenic  staphylococci 


DESCRIPTIONS   OF   PATHOGENIC   BACTERIA.    169 

and  streptococci  and,  on  the  other  side,  the 
great  differences  in  the  susceptibility  of  man, 
we  can  well  understand  how  these  widely  spread 
bacteria  may  produce  suppuration  of  the  in- 
ternal organs  or  multiple  external  abscesses  in 
one  person,  in  another  angina  or  catarrh  of 
the  mucous  membrane,  and  in  still  another 
rheumatic  processes.  It  may  be,  moreover, 
that  these  organisms  are  etiologically  con- 
cerned in  those  obscure  pathological  processes 
referred  to  "  catching  cold  "and  which  we  can 
hardly  speak  of  as  specific  diseases.  Bacteria 
of  this  sort  which  live  in  or  upon  sound  indi- 
viduals without  harming  them  may  be  called 
u  ceco-parasites."  If  any  weakening  of  the  tis- 
sues be  brought  about  by  privation,  or  any 
seat  of  disease  be  created  by  sudden  injury 
such  as  burning  or  freezing,  these  ubiquitous 
bacteria  take  advantage  of  such  a  local  pre- 
disposition to  display  their  pernicious  ac- 
tivity. 

Wherever  a  predisposition  exists  on  the 
part  of  the  tissues,  we  find  a  number  of  mi- 
crobes that  can  call  forth  inflammation  and 
suppuration.  In  inflammations  of  the  valves 
of  the  heart  there  are  found  under  various 
circumstances,  staphylococci,  streptococci,  or 
gonococci,  and  typhoid,  pneumonia  or  tubercle 
bacteria.  The  same  thing  is  true  in  certain 


I/O  BACTERIOLOGY. 

inflammations  of  the  joints  and  serous  mem- 
branes. 

If  the  tissues  have  become  altered  by  other 
diseases,  such  as  tuberculosis  or  scarlet  fever, 
staphylococci  or  streptococci  may  insinuate 
themselves  secondarily  and  produce  secondary 
diseases  or  mixed  infections  ;  thus  after  scarlet 
fever  there  are  often  found  diphtheritic  incrus- 
tations accompanied  by  the  presence  of  strep- 
tococci upon  the  mucous  membrane.  The 
destruction  of  lung  tissue  that  takes  place  in 
tuberculosis  is  brought  about  by  the  suppura- 
tion induced  by  staphylococci  and  streptococci. 
Koch  and  Gaffky  also  found  in  one  such  case 
Micrococcus  tetragenus,  a  coccus  grouped  tab- 
let-form in  blocks  of  four  and  surrounded  with 
a  capsule ;  it  is  perhaps  a  phase  in  the  life- 
cycle  of  a  sarcina,  and  should  therefore  more 
correctly  be  called  Merista  or  Sarcina  septica. 
It  stains  by  Gram's  method.  Its  growth  upon 
our  ordinary  culture  media  presents  no  strik- 
ing peculiarity.  It  does  not  liquefy  gelatin. 
On  inoculation,  white  mice  and  guinea-pigs 
succumb  with  a  sort  of  septicaemia,  while  gray 
mice  and  field  mice  appear  to  be  immune. 

Pneumonia. — Pasteur  first  cultivated  from 
ordinary  sputum,  and  Talamon  from  pneumoni- 
tic  sputum,  a  septic  bacterium  which  A.  Frankel 
proved  to  be  the  cause  of  true  fibrous  pneu- 


DESCRIPTIONS   OF   PATHOGENIC   BACTERIA.     171 

monia  in  man.  These  bacteria  are  often  lance- 
shaped,  and  are  frequently  grouped  in  pairs, 
for  which  reasons  the  organism  has  been  given 
the  name  Diplococcus  lanceolatus.  They  are 
arthrobacteria  and  stain  by  Gram's  method. 
They  are  so  sensitive  to  drying  that  a  few 
days'  desiccation  is  sufficient  to  render  them 
powerless.  When  shut  off  from  access  of  air, 
as  in  egg-cultures,  they  retain  their  virulence 
for  many  weeks  and  even  for  months,  and  their 
vitality  for  many  months  (Bunzl-Federn). 
They  cause  a  simple  typical  septicaemia  in 
rabbits  and,  when  virulent,  in  white  mice  and 
guinea-pigs  also,  but  for  the  latter  animals 
large  quantities  are  usually  necessary.  Dogs 
succumb  to  injection  with  the  toxin  but  not  to  in- 
fection. In  man  the  pneumococci  induce  typi- 
cal fibrous  pneumonia,  which  at  times  passes 
over  into  septicaemia ;  they  are  found  besides 
in  inflammations  of  the  serous  membranes,  of 
the  pleura,  of  the  cerebral  membranes,  and  in 
inflammations  of  the  middle  ear.  They  are 
found  also  living  as  oeco-parasites  in  healthy 
persons,  so  that  "  catching  cold  "  often  affords 
them  an  opportunity  of  invading  the  body.  In 
this  fact  lies  the  explanation  of  those  familiar 
instances  in  which  a  healthy  person  suddenly 
develops  pneumonia  as  a  consequence  of  tak- 
ing cold. 


1/2  BACTERIOLOGY. 

In  atypical  cases  of  lung-inflammation,  ery- 
sipelas streptococci  have  sometimes  been  found. 
Friedlander  found  also  an  arthrosporous  bac- 
terium which  develops  capsules,  and  in  which 
both  coccus  and  rod  forms  occur.  This  species 
is  called  Bacterium  capsulatum  pneumonia 
(Fig.  4,  D.);  it  loses  the  stain  in  Gram's  method. 
Upon  gelatin  it  shows  a  nail-shaped  growth 
and  the  gelatin  near  the  surface  is  colored 
brown  ;  in  contrast  to  the  Diplococcus  lance  ola- 
tus  it  is  rather  hardy.  It  causes  septicaemia 
easily  in  mice  and  guinea-pigs,  and  also  in 
rabbits  upon  the  injection  of  large  quanti- 
ties. 

It  is  seen  by  the  statements  already  made 
that  capsules  are  formed  occasionally  by  a 
number  of  bacteria,  as  for  instance  by  the  an- 
thrax bacteria.  Capsule  formation  also  takes 
place  regularly  in  certain  species  of  bacteria 
which  in  consequence  have  been  denominated 
"  capsule  bacteria."  The  type  is  Friedlander' s 
pneumo-bacillus.  Identical  with  this  organ- 
ism, and  differing  from  it  only  through  varia- 
tions in  virulence,  is  the  bacterium  of  rhino- 
scleroma,  first  seen  by  Fritsch  in  nasal  tumors, 
and  first  cultivated  by  R.  Paltauf  and  Eisels- 
berg.  A  bacillus  called  B.  crassus  sputigenus 
was  also  cultivated  by  Kreibohm  from  human 
sputum.  This  organism  proved  virulent  for 


DESCRIPTIONS   OF   PATHOGENIC   BACTERIA.    173 

mice  and  rabbits  ;  it  stained  by  Gram's  method. 
Another  capsule  bacillus  has  been  cultivated 
by  Weichselbaum  from  a  case  of  endocarditis 
with  purulent  infarction,  one  by  Mandry  out 
of  bronchial  mucus,  and  another  by  Kockel 
from  suppurated  hepatic  cysts  and  meningitis. 
Fasching  cultivated  a  capsule  bacillus  from 
the  purulent  mucous  membrane  of  the  naso- 
pharyngeal  space,  and  Abel  one  from  ozaena. 
All  of  these  reports  of  the  discovery  of  capsule 
bacilli  are  not  as  complete  as  they  should  be, 
but  R.  Pfeiffer  succeeded  in  cultivating  from 
the  peritoneal  exudate  of  a  guinea-pig  a  cap- 
sulated  species  which  actually  invested  the 
blood  and  tissue  juices  of  the  animal  under 
experiment  with  a  ropy  quality.  Chiari,  in  a 
case  of  cystitis  in  man,  which  led  to  suppurating 
inflammation  of  the  kidneys,  and  from  that  to 
pyaemia,  found  a  capsulated  bacterium,  gener- 
ally occurring  in  rod-form  ;  it  stains  by  Gram's 
method.  This  bacterium  is  fatal  to  white  mice, 
and  causes  pyaemia  on  subcutaneous  and  intra- 
peritoneal  inoculation  :  guinea-pigs,  inoculated 
subcutaneously,  develop  extensive  suppura- 
tion ;  and,  when  the  inoculation  is  intraperi- 
toneal,  peritonitis  and  general  infection  result ; 
rabbits,  inoculated  subcutaneously  develop 
suppuration,  when  inoculated  intravenously, 
septicaemia  and  when  the  kidneys  are  in- 


1/4  BACTERIOLOGY. 

jected,  suppurating  nephritis  with  ensuing 
septicaemia  occurs. 

Inflammation  of  the  membranes  of  the  brain 
can  be  produced  by  various  bacteria,  such  as 
Frankel's  pneumococcus,  the  streptococcus  of 
erysipelas,  tubercle  bacilli  and  B.  coli  corn- 
munis.  However,  Weichselbaum  and  later, 
H.  Jager,  have  made  it  appear  probable 
that  the  epidemic  form  of  cerebro-spinal  men- 
ingitis is  caused  by  a  particular  species,  the 
Diplococcus  intracellularis.  These  bacteria 
stain  by  Gram's  method,  both  in  cultures  and 
in  preparations  from  the  tissues,  but  in  sections 
become  decolorized  ;  they  form  capsules,  and 
are  cultivated  more  easily  than  the  lancet  bac- 
teria. White  mice  proved  refractory  to  in- 
oculation. The  experiments  with  the  organism 
are  not  yet  complete  enough  to  be  altogether 
convincing. 

The  bacteria  of  influenza  were  discovered  by 
R.  Pfeiffer  in  1891.  They  are  even  somewhat 
smaller  than  the  bacilli  of  mouse  septicaemia, 
about  two  to  three  times  as  long  as  they  are 
thick,  without  capsules,  and  are  decolorized  by 
Gram's  method.  They  grow  in  the  form  of  very 
fine  glassy  drops,  and  succeed  best  upon  blood- 
serum  or  blood-agar  or  when  haemoglobin  is 
added  to  the  medium.  A  similar  bacillus,  which 
can  be  cultivated  more  easily  and  is  called  the 


B  C 

Fig.  26. — A,  cholera  bacteria  in  the  blood  of  guinea  pigs  after  infec- 
tion of  the  small  intestine.     (From  photograph  by  van  Ermen- 
;  ghem)  i  :  700. 

B,  and  C,  The  Spirochaete  of  relapsing  fever  (after  photo- 
graphs), B,  I  :  700  ;  C,  I  :  IOOO. 


DESCRIPTIONS   OF   PATHOGENIC   BACTERIA.     175 

pseudo-influenza  bacillus,  is  perhaps  only  a 
variety  of  the  influenza  germ  which  has  become 
saprophytic  and  so  impotent.  Among  the 
lower  animals  only  the  ape  has  proved  suscep- 
tible to  inoculation  with  this  germ,  although 
rabbits  may  be  infected  with  large  num- 
bers of  the  bacteria  and  develop  fever  and 
paralysis.  Besides  la  grippe,  the  influenza 
organism  causes  in  man  atypical  lung  in- 
flammations, haemorrhages,  and  especially 
paralysis  and  persistent  muscular  weak- 
ness. 

A  true  septicaemia  is  caused  by  the  spiro- 
chsete  of  relapsing  fever  discovered  by  Ober- 
meier  in  1873.  The  germ  is  more  delicate 
in  structure  than  the  cholera  bacteria,  and  up 
to  the  present  time  is  known  only  in  the  form 
of  long  spirals,  and  not  in  the  S  or  comma  form 
(See  Fig.  26,  B,  C,  opposite).  Moczutkow- 
ski  has  successfully  infected  healthy  men 
with  blood  containing  the  spirochsete  and 
Carter  and  Koch  have  done  the  same  with 
apes,  thus  establishing  the  etiological  signifi- 
cance of  this  germ.  Attempts  to  cultivate  the 
spirochaete  have  not  yet  succeeded.  The  germs 
fail  to  retain  the  stain  in  Gram's  method. 
According  to  Metschnikoff  the  bacteria  are 
enveloped  during  the  fever-free  periods  and 
in  great  part  destroyed  by  the  cells  of  the 


1/6  BACTERIOLOGY. 

spleen    which   function    as    huge    devouring 
cells  or  "  macrophages." 

The  existence  of  animal  parasites,  especially 
Tcenice  and  Gregarinidce,  in  fishes  has  been 
known  for  some  time  ;  vegetable  parasites,  such 
as  Saprolegnia,  have  also  been  known;  and  like- 
wise the  fact  that  some  of  the  internal  organs 
of  fish,  particularly  the  sexual  organs,  are  poi- 
sonous. Mosso  discovered  that  the  blood  of 
the  eel  is  poisonous,  and  the  poisonous  quality 
of  putrid  fish  has  also  been  ascertained.  Fischel 
and  Enoch  found  in  1891,  while  working  in  my 
laboratory,  that  fishes,  too,  can  succumb  to  bac- 
terial infection.  They  discovered  that  a  disease 
affecting  carp  is  a  sort  of  septicaemia  accom- 
panied by  numerous  haemorrhages.  The  accom- 
panying bacteria  were  endosporous,  grew  upon 
gelatin,  agar,  blood-serum,  potato,  and  rice,  and 
stained  by  Gram's  method.  It  was  then  estab- 
lished for  the  first  time  that  these  bacteria  form 
the  same  proteid-like  poison  while  growing  as 
parasites  in  the  animal  body,  which  they  pro- 
duce saprophytically  in  cultures.  The  bacteria 
and  spores,  freed  from  poison,  infected  carp, 
mice  and  guinea-pigs,  and  the  animals  all 
perished  from  septicaemia.  The  poison  itself 
was  also  injurious  to  dogs,  which  sickened 
with  diarrhoea  in  the  same  fashion  observed  in 
the  "  carp  cholera."  Emmerich  and  Weibel 


DESCRIPTIONS   OF   PATHOGENIC    BACTERIA.    I// 

have  observed  in  trout  also  a  kind  of  septicae- 
mia caused  by  bacteria, 

The  germs  causing  gonorrhcea  and  blen- 
norrhcea  were  discovered  with  the  aid  of  the 
microscope  by  Neisser.  They  were  cultivated 
by  Bumm  upon  human  blood-serum  and  later 
were  studied  in  a  more  thorough-going  fashion 
by  Wertheim  especially  by  the  aid  of  the  blood- 
serum  plate  method  devised  by  Hueppe  ;  they 
grow  only  at  blood  temperature.  According 
to  Eraud  and  Hugounenq  they  secrete  a  poison- 
ous proteid-like  substance  when  grown  in  pep- 
tone solution,  but  not  when  in  asparagin  solu- 
tion. The  germs  are  biscuit-shaped  ;  they  give 
up  the  stain  when  treated  by  Gram's  method  ; 
both  these  characteristics  serve  generally  to 
distinguish  them  positively  from  the  Staphy- 
lococci.  They  are  usually  enclosed  in  the 
goriorrhceal  pus  cells  (Fig.25  A),  but  occur  also 
in  the  neighboring  organs,  and  are  found  in 
cases  of  peritonitis,  ovarian  inflammations,  in 
the  joints  in  gonorrhceal  rheumatism,  and  in  in- 
flammatory conditions  of  the  valves  of  the  heart. 

Nicolaier  in  1885  discovered  in  the  pus 
formed  in  cases  of  lockjaw  or  tetanus  rodlets 
which  form  endospores  at  one  end.  The  end  of 
the  rod  containing  the  endospores  is  broadened 
and  swollen,  giving  to  the  germ  the  shape  of  a 
drumstick.  Here,  therefore,  we  meet  with 


12 


178  BACTERIOLOGY. 

a  representative  of  the  genus  Plectridium.  In 
the  vegetative  stage  the  rods  often  elongate  into 
filaments  ;  they  stain  by  Gram's  method.  In 
gelatin  stab-cultures,  delicate  branches,  like 
those  of  a  fir-tree,  grow  out  from  the  inoculation 
line  into  the  gelatin ;  this  appearance  is  less 
marked  in  agar.  In  glucose-bouillon,  vigorous 
gas-production  takes  place  accompanied  by  a 
pronounced  turbidity  which  clears  gradually,  a 
deposit  settling  to  the  bottom.  The  gelatin  is 
slowly  liquefied  by  an  enzymotic  action.  The 
bacteria  are  anaerobic  and  in  cultures  develop 
a  repulsive  odor.  Growth  can  take  place  be- 
tween i5°-42° ;  spore  formation  can  occur 
within  the  same  temperature  limits,  but  at  the 
room  temperature  the  rod-forms  may  persist 
for  at  least  a  week  without  forming  spores. 
The  vegetative  cells  grow  poorly  above  42°  and 
perish  at  60°,  while  the  spores  are  very  resistant 
and  withstand  the  action  of  both  heat  and 
chemicals. 

,  Only  cultures  mixed  with  other  organisms 
cause  subcutaneous  suppuration ;  the  pure 
cultures  are  unable  to  do  this.  Perfectly  pure 
cultures  were  first  obtained  by  Kitasato  through 
the  application  of  a  method  based  on  the  resist- 
ance of  the  spores  to  heat,  and  by  Kitt  through 
anaerobiotic  methods.  A  powerful  poison,  in 
all  likelihood  of  a  proteid  character,  is  formed  in 


DESCRIPTIONS    OF   PATHOGENIC   BACTERIA.    1 79 

the  cultures.  The  bacteria  are  able  to  form 
this  toxin  synthetically  in  nutrient  media  free 
from  proteid  as  well  as  by  splitting  up  the  pro- 
teids  in  albuminous  media.  The  effect  pro- 
duced by  the  bacteria  upon  the  animal  or- 
ganism is  to  be  attributed  to  the  action  of 
the  poison,  since  the  effect  runs  parallel  with 
the  quantity  of  poison  carried  with  or  formed 
by  the  bacteria,  and  not  with  the  number  of 
bacteria  themselves.  The  poison,  like  strych- 
nine, acts  upon  the  spinal  cord  and  not  upon 
the  muscles  or  peripheral  nerves.  Mice, 
rabbits,  sheep  and  horses  are  susceptible,  fowls, 
dogs  and  men  somewhat  less  so.  Tetanus 
spores  when  alone  do  not  usually  germinate 
in  the  body,  but  they  can  germinate  when  in- 
troduced along  with  particles  of  soil  or  splinters 
of  wood,  or  with  pus.  Accordingly  infection 
in  this  disease  is  usually  a  mixed  infection, 
and  the  tetamis  bacillus  is  not  to  be  regarded 
as  a  strict  parasite.  In  the  soil  and  in  ooze 
it  may  perhaps  participate  in  the  marsh-gas 
fermentation. 

These  latter  statements  may  also  be  true  of 
the  bacteria  of  malignant  cedema.  These  or- 
ganisms were  first  described  by  Pasteur  as  the 
Vibrio  septique,  and  were  afterwards  studied 
accurately  by  Koch.  The  motile  rods  have 
flagella  on  the  ends  and  sides.  The  rods  grow 


180  BACTERIOLOGY. 

out  into  long  filaments  both  in  the  animal 
body  and  in  cultures  ;  they  are  decolorized  by 
Gram's  method.  During  spore-formation  the 
rods  become  spindle-shaped  ;  the  bacteria  be- 
long, therefore,  to  the  genus  Clostridium. 
They  are  anaerobic.  In  gelatin  they  grow  with 
vigorous  gas-production  ;  the  margin  of  the 
colonies  is  frayed  out  into  fine  rays,  and  the 
gelatin  is  gradually  liquefied.  In  agar  stab- 
cultures  also  the  colonies  show  branching.  In 
bouillon,  a  turbidity  makes  its  appearance 
followed  by  a  deposit  of  sediment.  The  effect 
brought  about  in  animals  by  subcutaneous  in- 
oculation is  to  be  attributed  not  so  much  to  the 
growth  of  the  bacteria  as  to  the  formation  of 
poison ;  only  after  the  death  of  the  host  has 
occurred  do  the  bacteria  multiply  very  much, 
but  then  they  multiply  even  in  the  blood, 
where  a  state  of  affairs  similar  to  that  in  anthrax 
may  sometimes  be  observed,  although  during 
life  the  blood  is  germ-free.  Subcutaneous  in- 
oculation in  guinea-pigs  gives  characteristic 
results :  the  animals  become  uneasy,  draw 
themselves  together  in  a  heap  and  cry  out  at 
the  slightest  touch.  Mice,  rabbits,  sheep, 
goats,  horses,  swine,  dogs,  fowls  and  ducks 
are  also  very  susceptible.  Man  is  moderately 
susceptible  ;  gangrenous  emphysema  is  some- 
times at  least,  caused  by  these  bacteria.  One 


DESCRIPTIONS   OF   PATHOGENIC   BACTERIA.    l8l 

instance  is  on  record  where  two  typhoid  fever 
patients,  who  were  infected  with  this  organism 
in  the  course  of  a  musk  injection,  perished 
from  oedema.  The  bacteria  of  oedema  are 
frequently  found  in  the  earth  and  in  marshy 
soil. 

The  disease  of  cattle  known  as  "  quarter- 
evil/'  "  black-leg  "  or  symptomatic  anthrax, 
the  bacillus  of  which  develops  subcutantously 
with  production  of  gas,  is  caused  by  bacteria 
which  resemble  those  of  malignant  oedema  in 
almost  all  points.  Infection  of  animals  is 
favored  by  the  simultaneous  introduction  of  lac- 
tic acid,  probably  because  this  substance  brings 
about  a  necrosis  of  the  cells.  It  is  fora  like  rea- 
son, probably,that  according  to  Roger,  the  nat- 
ural immunity  of  rabbits  to  this  disease  can  be 
overcome  if  the  metabolic  products  of  B.  prodi- 
giosus  or  of  Staphylococcus  be  injected  simultane- 
ously with  the  bacillus  of  symptomatic  anthrax. 
Cattle,  sheep,  goats  and  guinea-pigs  are  espe- 
cially susceptible,  horses,  asses  and  white  rats 
less  so,  while  swine,  dogs,  rabbits,  gray  rats, 
ducks,  pigeons,  and  fowls  appear  to  be  immune. 
Sometimes,  for  example  in  reciprocal  protec- 
tive inoculation,  there  appears  to  exist  nothing 
but  a  difference  in  virulence  between  the  bac- 
teria of  malignant  oedema  and  those  of  symp- 
tomatic anthrax,  but  the  question  of  actual 


1 82  BACTERIOLOGY. 

identity  must  be  regarded  as  still  an  open  one. 
Symptomatic  anthrax  was  formerly  regarded 
as  a  form  of  anthrax  till  Feser  and  Bollinger 
determined  its  true  specific  nature  in  1876  ; 
Arloing,  Cornevin,  and  Thomas  were  the  first 
to  obtain  cultures. 

In  diphtheria,  rods  were  first  observed  mi- 
croscopically by  Klebs,  and  in  1884  Lo filer 
succeeded  in  cultivating  them  on  artificial 
media.  The  rods  take  stain  badly  and  are 
easily  plasmolyzed,  so  that  usually  the  ends  of 
the  rods  stain  more  plainly  than  the  middle,  or, 
sometimes,  the  staining  of  a  number  of  gran- 
ules gives  a  beaded  appearance  to  the  cell. 
The  bacteria  retain  the  stain  when  treated  by 
Gram's  method.  The  rods  are  localized  in  the 
diphtheritic  patches  upon  mucous  membranes 
and  are  not  dispersed  through  the  body.  The 
effect  produced  by  their  presence  upon  the 
animal  organism  is  therefore  due  to  the  forma- 
tion of  poison.  The  poison  was  at  first  re- 
garded by  Roux  and  Yersin  as  an  enzyme, 
and  by  Brieger  and  Frankel  as  a  toxalbumin ; 
it  is  formed  in  media  containing  proteid  and  also 
in  solutions  devoid  of  proteid,  as  in  ammonium 
lactate  or  asparagin  (Uschinsky),  and  in  pro- 
teid-free  urine  (Guinochet) ;  and  even  after  the 
formation  of  the  toxin,  no  proteid  reaction  is  ob- 
tained from  these  media  ;  the  proteid  nature  of 


DESCRIPTIONS   OF   PATHOGENIC   BACTERIA.    183 

the  poison  is  consequently  doubtful  (cf.  p.  123). 
Endospores  have  not  been  observed,  and  C. 
Frankel  has  noticed  occasional  branched  fila- 
ments. It  is,  then,  evident  that  the  position  of 
the  diphtheria  germ  in  our  system  of  classifica- 
tion is  not  clear ;  in  any  case,  the  germ  is  not  a 
typical  bacillus.  Cultures  develop  between  18° 
— 42°,— best  in  blood  serum  to  which  bouillon 
and  sugar  have  been  added,  not  so  well  upon 
glycerin  agar.  The  colonies  are  white  and 
usually  remain  distinct  from  one  another ;  up- 
on serum  is  formed  a  delicate  white  incrusta- 
tion ;  in  gelatin  stab-cultures  a  scanty  growth 
develops  in  the  form  of  small  white  colonies. 
In  broth,  small  grayish  crumbs  are  formed 
which  sink  to  the  bottom  ;  rarely  a  diffuse 
clouding  occurs;  milk  is  coagulated  by  the 
growth  of  the  bacteria.  Guinea-pigs  are  es- 
pecially sensitive  to  inoculation ;  somewhat 
less  so  are  rabbits,  young  dogs,  sheep,  goats, 
horses,  pigeons,  and  fowls.  (The  ordinary 
spontaneous  diphtheria  of  fowls  and  pigeons  is 
an  altogether  different  disease).  In  the  ani- 
mals named  above  there  arises,  just  as  in  man, 
a  necrotic  inflammation  of  the  mucous  mem- 
brane and,  proceeding  from  this,  an  acute 
poisoning  often  accompanied  by  paralysis. 
The  diphtheria  bacteria  have  been  found  in 
man  in  the  diphtheritic  incrustation  of  the 


1 84  BACTERIOLOGY. 

mucous  membrane,  in  conjunctivitis  fibrin osa, 
and  (by  Abel)  in  wound  diphtheria.  Virulent 
diphtheria  bacteria  have  also  been  observed, 
existing  as  ceco-parasites  in  healthy  individ- 
uals;  these  may,  under  special  conditions,  in- 
duce self-infection  or  be  the  means  of  conveying 
the  disease  to  susceptible  persons,  particularly 
to  children. 

Virulent  diphtheria  germs  lose  their  viru- 
lence under  cultivation,  especially  in  agar  cul- 
tures, while  their  growth  becomes  at  the  same 
time  more  luxuriant,  that  is  to  say,  more  sap- 
rophy  tic.  Similar  but  non-virulent  bacteria  are 
sometimes  found  occurring  spontaneously  in 
man,  Loffler  being  the  first  to  discover  this  fact. 
Many  bacteriologists,  among  them  Roux,  Yer- 
sin,  C.  Frankel,  and  Hueppe,'  regard  these 
so-called  pseudo-diphtheria  bacilli  merely  as 
true  diphtheria  germs  which  have  become  im- 
potent and  saprophytic,  while  Loffler,  Hof- 
mann,  von  Wellenhof  and  Escherich  regard 
them  as  a  totally  distinct  species.  The  pseudo- 
diphtheria  germs  do  not  alter  the  reaction  of 
alkaline  bouillon  while  the  diphtheria  bacteria 
render  it  acid  at  the  outset,  but  it  afterwards 
becomes  again  alkaline. 

Cholera  asiatica.  The  so-called  comma 
bacilli  found  in  this  disease  were  discovered  by 
Koch  in  1883  (Fig.  27).  They  occur  in  the  form 


DESCRIPTIONS   OF   PATHOGENIC   BACTERIA.    185 


Fig.  27.  Cholera  asiatica. 

J,  Comma  bacilli,  1-4  after  drawings  ;  4,  twisted  coil,  so-called 
Spirodiscus,  (about  I  :  1200)  ;  5,  6,  spiral  filaments  with  spir- 
ulina  twistings  (after  photographs,  about  i  :  700). 

B.  Ripe  arthrospores  (after  photographs),  about  i  :  1000. 

C.  i  and  2,  Arthrospores  in  filaments  (after  van  Ermenghem, 
from  photograph),  about  I  :  700. 

3-7,  germinating  arthrospores  (after  photographs  by  Pertik, 
I  :  1200). 

of  rods  curved  like  a  comma  and  frequently  bent 
far  around  like  a  crescent ;  often,  however,  they 
appear  perfectly  straight.  They  grow  out  in- 
to S  forms  and  long  corkscrew  filaments,  the 
spirals  of  which  are  sometimes  closely,  some- 
times loosely  wound.  Both  the  formation  and 
germination  of  arthrospores  have  been  ob- 
served. On  our  system  of  classification,  then, 


1 86  BACTERIOLOGY. 

they  should  be  classed  as  Spirock&te.  Metsch- 
nikoff  claims  to  have  observed  branched  fila- 
ments also,  so  that  the  comma  bacillus  may 
perhaps  belong  in  the  cycle  of  development  of 
some  species  of  Cladothrix,  a  group  in  which 
all  forms  of  comma  bacilli  have  been  actually 
observed  by  Zopf  (cf.  Fig.  5).  The  germs  are 
decolorized  by  Gram's  method.  In  the  intes- 
tine they  occur  not  only  free,  but  also  in  the 
epithelium  (Fig.  250),  and  can  even  penetrate 
into  the  wall  of  the  intestine  itself  as  far  as 
the  muscular  layer.  Further  penetration, 
however,  ensues  only  in  fatal  cases,  and  then 
only  immediately  before  death  ;  the  germs  are 
as  a  rule,  however,  found  in  the  gall-bladder ;  in 
animal  experiments,  both  when  inoculated  into 
the  peritoneal  cavity  or  into  the  stomach,  they 
may  occasionally  pass  over  into  the  blood,  in 
which  they  sometimes  appear  like  the  Spiro- 
ch&te  of  relapsing  fever  (Fig.  26  A).  The  ef- 
fect produced  in  man  depends  less  upon  their 
proliferation  in  the  intestine  and  in  the  intes- 
tinal epithelium  than  upon  the  formation  of  a 
toxin  which,  with  concomitant  lowering  of  the 
body  temperature,  proves  fatal  to  men  and  sus- 
ceptible animals.  This  proteid-like  poison  can 
be  formed  not  only  analytically  but  syntheti- 
cally also,  as  for  example  out  of  ammonium 
lactate  and  asparagin.  The  toxin  has  been 


DESCRIPTIONS   OF   PATHOGENIC    BACTERIA.    187 

obtained  from  cultures  by  Hueppe,  Scholl  and 
Petri.  (Hueppe  first  obtained  it  from  the  bodies 
of  cholera  patients  in  1892,  and  Bosc  likewise 
found  the  poison  in  1895  in  the  bodies  of 
cholera  patients.)  R.  Pfeiffer  has  attempted  to 
identify  the  poisonous  action  of  virulent  comma 
bacilli  with  the  effect  of  their  cell  proteid,  and 
has  accepted  the  theory  of  Cantani  that  it  is  not 
the  living  comma  bacilli  which  through  their 
formation  of  poison,  are  the  effective  agents, 
but  rather  the  dead  comma  bacteria  by  virtue  of 
the  action  of  their  poisonous  body-substance. 
The  cholera  toxin  is  not,  however,  identical  with 
the  proteid  of  the  bacterial  cell ;  the  effect  due 
to  the  action  of  the  latter  substance  is  mani- 
fested also  by  various  forms  of  impotent  comma 
bacilli,  but  the  toxin  is  formed  only  by  the 
virulent  variety. 

The  cholera  bacteria  grow  in  gelatin  in  the 
form  of  colonies  which  appear  like  fine  frag- 
ments of  glass  or  a  tangle  of  glass  threads ; 
they  liquefy  the  gelatin  slowly.  This  initial 
character  of  their  growth  in  gelatin  is  tolerably 
distinctive,  yet  many  colonies  grow  rapidly, 
others  more  slowly.  In  consequence  of  such 
atypical  growth,  diagnosis  is  often  quite  diffi- 
cult, and  it  is  frequently  necessary  to  postulate 
the  existence  of  varieties  of  the  species.  Cul- 
tures obtained  from  an  outbreak  of  cholera  in 


1 88  BACTERIOLOGY. 

Massowah  especially  are  to  be  separated  from 
cultures  of  cholera  germs  obtained  in  European 
epidemics. 

In  peptone  solutions  the  bacteria  produce 
indol  and  also  reduce  nitrate  to  nitrite  ;  conse- 
quently on  the  addition  of  hydrochloric  or  sul- 
phuric acid  the  nitroso-indol  reaction  takes 
place  in  the  form  of  a  rose-red  coloration  which 
has  been  named  the  "  cholera-red  "  reaction. 
In  ordinary  bouillon  a  pellicle  is  formed  on  the 
surface,  in  glucose-bouillon  this  does  not  occur. 
On  potato  at  high  temperatures  a  yellowish- 
brown  pigment  is  formed ;  in  milk  a  rennet- 
like  separation  into  curd  and  whey  is  some- 
times produced.  The  differential  diagnosis  of 
cholera  has  become  very  difficult  becatise  many 
comma  bacilli  have  been  found  which  grow  in 
gelatin  and  bouillon  very  much  like  the  typical 
and  atypical  varieties  of  cholera  bacteria. 

In  the  lower  animals,  no  spontaneous  cases 
of  any  disease  caused  by  Koch's  cholera  bacteria 
'have  ever  been  observed ;  when  inoculated 
artificially,  however,  virulent  germs  prove  infec- 
tious for  guinea-pigs  and  often  also  for  pigeons  ; 
in  the  latter  animals  the  toxic  disease  passes 
into  a  septicsemic.  Another  comma  bacillus 
nearly  related  to  Koch's,  which  was  found  by 
Gamaleia  in  a  fowl  epidemic  and  named  after 
Metschnikoff ,  is  infectious  for  animals  ;  pigeons 


DESCRIPTIONS    OF   PATHOGENIC   BACTERIA.    189 

especially  succumb  easily.  These  bacilli  give 
the  cholera-red  reaction  and  resemble  Koch's 
bacteria  in  other  respects  as  well. 

The  comma  bacilli  of  Finkler-Prior  do  not 
afford  the  cholera-red  reaction  since,  although 
they  form  indol,  they  do  not  reduce  nitrates. 
Upon  potato  at  the  room  temperature  they 
develop  a  yellowish,  slimy  incrustation.  The 
comma  bacilli  cultivated  by  Deneke  from 
cheese  likewise  give  no  cholera-red  reaction ; 
they  produce  in  milk  a  sulphur-yellow  pig- 
ment. In  the  rivers  Spree,  Elbe  and  Seine, 
comma  bacilli  have  been  found  which  behave 
exactly  like  Koch's  bacteria.  These  water 
bacteria,  it  is  true,  are  phosphorescent,  while 
the  cholera  bacteria  are  not  generally  so,  but 
Rumpel l  has  twice  cultivated  luminous  comma 
bacilli  from  cases  of  cholera,  and  on  the  other 
hand,  phosphorescent  comma  bacilli  may  lose 
their  phosphorescence,  although  still  remain- 
ing pathogenic.  From  a  case  of  summer 
diarrhoea  occurring  in  Bohemia,  Zorkendorfer 
cultivated  a  species  which  was  neither  infec- 
tious nor  gave  the  cholera-red  reaction. 

The  virulence  of  the  cholera  bacteria  varies 
extraordinarily  and  this  fact  has  given  rise  to 
much  controversy.  Under  saprophytic  condi- 
tions of  life,  as  in  water,  for  instance,  the  germs 

1  Berl.  klin.  Wochenschr.,  1895,  No.  4. 


190  BACTERIOLOGY. 

lose  their  virulence,  and  this  change  comes 
about  more  quickly  in  pure  water  than  in 
polluted  water.  Infection  on  the  other  hand  is 
favored  by  a  diseased  condition  of  the  mucous 
lining  of  the  stomach,  and  Metschnikoff  has 
discovered  that  the  infection  of  animals  can  be 
accomplished  more  easily  if  other  microbes  are 
inoculated  simultaneously  with  the  cholera 
germ. 

Intestinal  alterations  like  those  observed  in 
cholera  may  also  be  brought  about  by  the  intra- 
venous inoculation  of  putrid  fluids,  as  Hem- 
mer,  Virchow,  and  many  others  noticed  long 
ago.  R.  Fischel  observed  similar  appearances 
in  children,  as  a  consequence  of  sepsis. 

Cholera  nostras.  This  disease  is  not  to  be 
attributed  to  a  single  bacterial  species.  The 
fact  seems  to  be  that  several  ceco-parasites, 
under  special  conditions  which  serve  to  create 
a  predisposition,  become  able  to  invade  the 
body,  multiply  there  and  form  poison.  A  case 
of  this  sort  was  communicated  by  me  in  1887: 
a  person,  after  drinking  very  cold  beer  while 
irr  a  heated  condition,  became  the  subject  of  a 
violent  cholera-like  attack  with  typical  rice- 
water  stools,  an  effect  that  was  brought  about 
by  the  ordinary  colon  bacillus,  B.  coli  com- 
munis.  The  same  bacteria  have  been  sub- 
sequently often  found  in  summer  diarrhoea, 


DESCRIPTIONS   OF   PATHOGENS   BACTERIA.    IQI 

indeed,  they  were  regarded  by  Emmerich  as 
the  cause  of  Asiatic  cholera.  Cases  of  cholera 
nostras  in  which  the  comma  bacilli  of  Finkler- 
Prior  were  found,  have  been  recorded  by  Fink- 
ler-Prior,  Lustig,  Gruber,  Ruete  and  Enoch. 
Zorkendorfer  found  in  one  case  still  a  different 
kind  of  comma  bacillus,  and  in  another  case 
Beck  found  streptococci. 

Typhoid  Fever.  The  bacteria  of  this  disease 
were  first  demonstrated  microscopically  by 
Eberth  and  Koch,  and  in  1884  were  cultivated 
by  Gaffky.  They  are  short  plump  rods  with 
rounded  ends,  often  joined  in  filaments.  They 
stain  in  sections  less  readily  than  many  other 
bacteria,  and  in  consequence  of  plasmolysis 
show  granulation  and  polar  granules.  Endo- 
genous spores  are  not  found,  so  that  the  germs 
must  be  placed  with  the  arthrobacteria.  Gram's 
coloration  is  negative.  They  are  actively  mo- 
tile and  possess  flagella  on  the  ends  and  sides. 
The  size  of  the  rods  varies  very  greatly  and 
according  to  the  media  in  which  they  are 
growing.  They  grow  at  the  room  and  at  blood 
temperatures  and  are  not  fastidious  about  their 
food-substance.  Upon  gelatin  they  form  white, 
irregular,  often  leaf-shaped  colonies  which 
spread  over  the  surface  in  a  fine  iridescent 
film.  Upon  certain  potatoes  they  do  not  grow 
at  all,  upon  some  they  form  a  delicate  yellow 


IQ2  BACTERIOLOGY. 

brown  coating.  As  a  rule,  however,  they  spread 
out  upon  the  potato  in  the  form  of  an  invisible 
film  the  existence  of  which  is  made  apparent 
to  the  observer  only  through  the  increased  glis- 
tening of  the  surface.  This  growth  on  potato 
is  usually  characteristic,  but  unfortunately  it 
is  not  constant  and  is  observed  occasionally  in 
other  species,  so  that  differential  diagnosis  of 
the  typhoid  bacteria  is  at  times  very  difficult. 
Many  saprophytic  species  from  water  and  soil 
grow,  especially  upon  gelatin,  very  much  in 
the  manner  of  the  typhoid  bacillus  and  can 
ordinarily  be  distinguished  from  it  only  by 
such  characters  as  individual  form,  behavior 
towards  Gram's  stain,  motility,  and  growth 
upon  potato. 

It  is  often  extraordinarily  difficult  to  distin- 
guish the  typhoid  bacillus  from  B.  coli  com- 
munis.  Microscopically  and  culturally  the  dif- 
ference is  inconsiderable.  The  greatest  pains 
have  been  taken  to  discover  fundamental  dif- 
ferences. As  a  rule  B.  coli  forms  a  dirty- 
yellow  incrustation  upon  a  piece  of  a  potato 
on  which  the  typhoid  bacillus  grows  in  the 
form  of  an  invisible  film.  B.  coli  generally 
coagulates  milk  and  the  typhoid  bacillus  does 
not ;  in  glucose  solutions  vigorous  gas-produc- 
tion is  brought  about  by  B.  coli,  but  not  by 
the  typhoid  bacillus  ;  B.  coli  forms  indol  out  of 


DESCRIPTIONS   OF   PATHOGENIC    BACTERIA.    193 

peptone,  while  the  typhoid  bacillus  does  not, 
so  that  when  potassium  nitrite  and  sulphuric 
acid  are  added  to  both  cultures  a  rose-red  colo- 
ration appears  in  the  culture  of  the  former,  and 
not  in  that  of  the  latter.  B.  coli  forms  dextro- 
rotatory, the  typhoid  bacillus  laevo-rotatory 
lactic  acid  out  of  milk-sugar.  The  reduction 
of  nitrates  to  ammonia  is  accomplished  by  both 
species.  However,  many  of  these  statements 
are  positively  contradicted  by  some  observ- 
ers. 

There  are  in  fact  at  present  two  opposing 
views.  The  one  which  to  me  seems  to  be  the 
better  founded  is  that  the  bacteria  of  typhoid 
fever  and  B.  coli  communis  are  two  distinct 
species.  The  other  view  is  that  the  common 
intestinal  saprophyte,  B.  coli  communis,  is  an 
ceco-parasite  which,  under  special  conditions, 
may  become  able  to  invade  the  body,  and 
penetrate  into  the  living  organism  where  it 
undergoes  transformation  into  the  typhoid  bac- 
terium. 

Both  kinds  of  bacteria  are  usually  not  in- 
fectious for  the  lower  animals,  but  as  a  rule 
merely  toxic ;  only  when  the  bacteria  are  very 
virulent  does  a  multiplication  take  place  in 
living  rabbits  and  mice.  The  "  true  "  typhoid 
bacteria  produces  typhoid  fever  in  man,  pene- 
trating from  the  intestine  into  the  Peyer's 
13 


194  BACTERIOLOGY. 

patches  and  thence  into  the  mesenteric  glands 
and  the  spleen.  They  are  found  in  the  rose- 
spots  on  the  abdomen,  but  the  circulating 
blood  is  usually  free  from  them.  They  may 
induce  also  broncho-pneumonia,  meningitis, 
myocarditis,  orchitis,  and  especially  suppura- 
tions such  as  otitis,  periostitis,  peritonitis  and 
empyema.  They  may  also  produce  inflamma- 
tion of  the  kidneys,  and  I  have  cultivated 
them  from  the  urine  during  life  in  cases  where 
albuminuria  occurs,  while  A.  Pfeifferhas  culti- 
vated them  from  the  diarrhceal  stools,  where 
they  generally  appear  only  after  the  first  week 
of  the  disease. 

The  "  true  "  colon  bacteria  have  been  re- 
peatedly observed  in  pneumonia  in  children 
and  also  in  inflammatory  processes  in  the  in- 
testine, especially  in  inflammation  of  the  ap- 
pendix and  in  perforation-peritonitis  ;  also  in 
otitis,  puerperal  fever,  and  more  often,  in  in- 
flammations of  the  bladder  when  inflammation 
ascending  to  the  kidney  may  be  induced. 

The  typhoid  bacteria  have  been  found  in  the 
water  of  wells,  especially  in  the  slime  at  the 
bottom,  and  once  also  they  have  been  found  in 
soil ;  the  colon  bacteria  are  often  found  in  pol- 
luted water. 

In  cases  of  meat-poisoning,  bacteria  are  usu- 
ally found  which  bear  a  striking  resemblance 


DESCRIPTIONS    OF   PATHOGENIC    BACTERIA.    195 

to  the  colon  bacillus.  A.  Gartner T  has  isolated 
a  species  which  has  frequently  been  found  in 
cases  of  poisoning  from  meat,  sausage  and 
milk.  In  cultures,  however,  after  about  two 
transfers,  a  difference  in  the  behavior  toward 
stains  makes  its  appearance.  The  colon  bac- 
terium generally  shows  polar  granules,  but  in 
Gartner's  bacterium,  after  staining  with  gen- 
tian-violet and  decoloration  with  2  per  cent, 
acetic  acid,  the  middle  portion  remains  colored. 
In  the  epidemic  of  bubonic  plague  occur- 
ring in  China,  in  1894,  bacteria  were  found  by 
Yersin  and  Kitasato  which  occur  in  the  form  of 
cocci  and  short  rodlets,  and  belong  therefore  to 
the  genus  Arthrobacterium.  The  character- 
istic growth  of  the  microbes  upon  agar  and 
gelatin  has  not  been  communicated  up  to  this 
time.2  In  man  they  are  found  at  first  in  the 

1  Correspondenz-Blatt  d.  allg.   arztl.    Ver.   von  Thiiringen,  1888, 
No.  9. 

2  There  seems  still  to  be  some  uncertainty  respecting  the  identity 
of  the  germs  originally  described  by  Kitasato  and  Yersin.     (Ogata, 
Centralbl.  f.  Bakt,  XXI.,  1897,  p.   769).     The  plague  bacillus  that 
has  found  its  way  to  bacteriological  laboratories  and  with  which 
successful  inoculation  experiments  have  been  made  has  well-defined 
characters.     It  is  rod-shaped,  and  is  about  i/z  in  diameter,  though 
varying  considerably  in  length  and  exhibiting  marked  pleomorphism. 
It  is  wholly  without  the  power  of  independent  movement.  It  stains 
easily  with  the  ordinary  aniline  dyes,  but  is  decolorized  by  Gram's 
method.     Growth  occurs  readily  on   the  ordinary  nutrient   media. 
On  agar,  white  circular   colonies,  somewhat   transparent   and   with 
iridescent  edges,  are  formed.     The  germ  multiplies  best  at  about  the 
temperature   of   the   human  body,  though   it  also   grows   at  8°-io° 


10  BACTERIOLOGY. 

buboes,  thence  they  extend  into  the  lymphatic 
glands  and  shortly  before  death  are  found  in 
rare  instances  and  in  small  numbers  in  the 
blood.  Subcutaneous  inoculation  of  rats,  mice 
and  rabbits,  causes  these  animals  to  sicken  with 
formation  of  buboes ;  J;he  animals  also  succumb 
to  stomach  infection  with  virulent  ctiltures 
taken  directly  from  man.  An  epidemic  among 
rats  preceded  the  epidemic  of  the  plague  in  that 
quarter  of  Hong  Kong  lately  visited  by  the 
scourge  ;  buffalo  and  swine  also  sickened  sim- 
ultaneously. The  question  of  the  mode  of 
transmission  of  the  disease  is  still  obscure; 
one  well-supported  possibility  is  that  of  the 
conveyance  of  contagion  by  flies. 

"  Mouse  typhoid "  is,  according  to  LofHer,1 
caused  by  an  anaerobic,  arthrosporous  bacter- 
ium which  grows  slowly  beneath  the  surface  of 
gelatin.  In  the  interior  of  the  gelatin  it  de- 

Spore  formation  has  not  been  observed.  Under  favorable  con- 
ditions of  moisture,  temperature,  etc.,  the  plague  bacillus  may 
survive  for  a  long  time  outside  of  the  animal  body.  (For  a  good 
description  of  the  characters  of  this  bacillus  cf.  Abel,  Zur  Kennt- 
niss  des  Pestbacillus,  Centralbl.  f.  Bakt.,  XXL,  1897,  p.  497,  and  the 
paper  of  Ogata  cited  above.) 

Rats,  mice,  guinea-pigs  and  rabbits  are  susceptible  and  manifest 
symptoms  closely  resembling  those  of  the  bubonic  plague  in  man. 
Animals  such  as  rats  are  naturally  infected  and  probably  play  an 
important  part  in  the  dissemination  of  infection.  An  anti-plague 
serum  has  been  prepared  by  Yersin  and  Calmette,  and  has  been 
used  with  distinct  success  in  parts  of  China  and  India.  E.  O.  ]. 

1  Centralbl.  f.  Bakt,  XL,  1892,  p.  130. 


DESCRIPTIONS    OF   PATHOGENIC    BACTERIA.    197 

velops  delicate  white  fleecy  clouds  which,  be- 
come diffused  through  the  medium.  In  agar 
yellow-white  colonies  limited  in  extent,  arise. 
The  small  rods  are  like  needle-shaped  crystals, 
0.8-i.u  long,  O.I-0.2/'-  thick,  and  are  often 
grouped  in  pairs  ;  they  are  not  motile. 
These  bacteria  are  interesting  from  the  fact 
that  LofHer  used  them  successfully  in  com- 
bating a  plague  of  mice  in  Thessaly.  The 
cultures  were  smeared  upon  bread  which  was 
distributed  over  the  fields  so  the  mice  might 
feed  upon  it,  the  bacteria  having  proved  to  be 
harmless  for  all  the  animals  experimented 
upon  save  mice. 

Tuberculosis.  Tumors  in  connective  tissue 
may  occur  in  the  form  of  nodules  or  tubercles 
varying  from  the  size  of  a  millet  seed  and  un- 
der to  the  size  of  a  pigeon's  egg.  By  the  term 
tuberculosis,  however,  is  understood  a  definite 
kind  of  nodule  formation  which  shows,  besides 
small  cells,  epithelioid  cells  (Fig.  25  E),  and 
often  giant  cells,  and  is  caused  by  an  organism 
studied  microscopically  by  Koch  and  Baum- 
garten  in  1882.  The  organism  was  also  cul- 
tivated, and  was  more  accurately  and  fully  in- 
vestigated by  Koch  (Fig.  28.).  The  rods  are 
often  plainly  enclosed  in  a  sheath,  inside  of 
which  are  found,  along  with  the  rods,  whole 
series  of  cocci  formed  as  the  result  of  plasmo- 


198 


BACTERIOLOGY. 


Fig.  28. — The  Germ  of  Tuberculosis. 

a,  ordinary  forms  found  in  cultures  and  sputum  (after  photo- 
graphs), about  i  :  900. 

b,  Shows  plasmolyzed  cell  contents,  so-called  coccothrix  forms 
(i  :  1250;. 

c,  portion  of  the  edge  of  a  fresh  culture  of  the  germ  of  mam- 
malian tuberculosis,  unstained  (about  i  :  2000). 

d,  stained,  1-3,  after  photographs  by  F,  Fi&chel,  i,  the  germ  of 
aviari  tuberculosis  from  glycerin  agar,  2,  3,  the  germ  of  mam- 
malian tuberculosis  from  egg  cultures  ;  4,  mammalian  cultures 
from  glycerin  agar,  Hayo  Bruns.  (1-3,  about  i  :  1200  ;  4,  i  :  1000) 
e,  g,  h,  Formation  of  Chlamydospores  ;  e,  mammalian  tubercu- 
losis (after  photographs,  i  :  9000)  ;  g,  from  sputum  (drawing 
after  Coppen  Jones,  i  :  1250)  ;  h  chlamydospores  of  Mucor  for 
comparison.    jF,  branching  of  filaments  (after  Coppen  Jones), 
I  :  1250  ;  at  x  it  can  be  seen  that  the  vacuoles  extend  from  the' 
main  stem  into  the  side  branches,  as  in  k,  a  hypha  of  Peniciilium 
thus  showing  the  existence  of  "  true  "  branching. 


DESCRIPTIONS   OF   PATHOGENIC   BACTERIA.    199 

lysis.  The  rods  develop  filaments  which  ex- 
hibit true  branching  ;  the  branches  often  show 
club-shaped  buds.  There  are  no  endospores 
as  was  at  one  time  claimed,  Koch  having 
mistaken  vacuoles  for  spores.  On  the  other 
hand,  according  to  Coppen-Jones  chlamy do- 
spores  are  actually  formed.  The  so-called 
tubercle  bacillus  is  consequently  not  a  bacillus 
at  all,  but  the  parasitic  growth-form  of  a  pleo- 
morphic  mould.  .' 

The  cultures  grow,  although  slowly,  upon 
bouillon,  blood  serum,  and  agar,  and  thrive  best 
when  glycerine  is  added  to  these  media.  The 
bacteria  when  derived  from  man  and  other  mam- 
mals generally  grow  more  slowly  than  those  ob- 
tained from  the  body  of  fowls.  Growth  is  first 
apparent  in  the  former  after  14  days,  in  the  lat- 
ter after  8  days  ;  the  former  develop  dry  scales, 
the  latter  a  somewhat  moister  and  smoother 
film;  the  former  grow  between  29°-42°,  the 
latter  between  25°-44°.  Hueppe  and  Fischel, 
by  varying  the  conditions  of  cultivation,  have 
so  modified  the  mammalian  germ  that  it  grew 
like  the  germ  of  fowl  tuberculosis,  and  the  latter 
like  the  germ  of  mammalian  tuberculosis. 
The  virulence  also  was  influenced  in  such  a 
way  that  mammals  could  be  infected  by  the 
bacteria  of  fowl  tuberculosis  and  vice  versa. 
Consequently,  the  view  of  Maffucci  and  Koch 


2OO  BACTERIOLOGY. 

that  there  are  two  different  species  or  varieties 
of  bacteria,  one  of  which  causes  mammalian,  the 
other  avian  tuberculosis,  falls  to  the  ground. 
The  two  kinds  are  simply  nutritional  modifi- 
cations, the  one  being  adapted  to  the  mamma- 
lian organism,  the  other  to  the  avian  organism 
which  is  endowed  with  a  somewhat  higher  tem- 
perature. Fischel  cultivated  from  the  body  of 
an  ape  bacteria  which  were  in  no  wise  different 
from  the  bacteria  of  avian  tuberculosis,  and  I 
have  cultivated  bacteria  from  fowl  and  pheas- 
ants which  bore  all  the  characteristic  marks 
of  the  germ  of  mammalian  tuberculosis. 

In  man  the  micro-organism  is  found  in  simple 
miliary  tuberculosis,  in  tuberculosis  of  the 
skin  and  in  lupus,  in  scrofula  and  tuberculosis 
of  the  joints  ;  when  in  the  lungs  in  association 
with  various  pus-producing  bacteria,  it  produces 
lung-consumption.  The  clinical  conceptions 
phthisis  and  lupus  therefore  need  to  be  further 
defined  to  accord  with  their  etiology,  i.  e.,  we 
must  distinguish  tuberculous,  carcinomatous, 
or  syphilitic  phthisis  and  tuberculous  or  carci- 
nomatous lupus  ;  the  unqualified  terms,  phthi- 
sis and  lupus  always  mean  at  present  the  re- 
spective forms  caused  by  the  tubercle  bacillus. 
Experiments  upon  animals  show  that,  besides 
simple  tuberculosis,  the  bacteria  induce  also 
simple  phthisis  and  suppuration. 


DESCRIPTIONS    OF   PATHOGENIC    BACTERIA.    2OI 

If  tubercles  occur  in  which,  instead  of  the 
tubercle  bacillus,  other  bacteria  are  found  the 
affection  is  called  pseudo-tuberculosis.  Ma- 
lassez  and  Vignal  have  observed  an  affection 
of  this  sort  which  is  caused  by  cocci,  A.  Pfeiffer 
and  Eberth  one  by  rod-forms,  Fischel  one  by 
filamentous  bacteria  and  Eppinger  one  by  a 
Cladothrix.  Non-communicable  tubercles  may 
be  produced  also  by  the  eggs  of  distomes  and 
by  other  foreign  bodies ;  even  dead  tubercle 
bacilli  may,  according  to  Prudden,  cause  tu- 
bercle formation. 

Tuberculosis  occurs  spontaneously  in  apes 
as  well  as  in  man,  and  also  in  cattle.  (In 
these  animals  the  form  of  pleural  tuberculosis 
with  a  tendency  to  calcification  is  called  by 
the  special  name  Perlsucht ;  the  rods  found 
here  are  somewhat  smaller  and  more  pointed.) 

The  disease  occurs  also  in  guinea-pigs  and 
rabbits.  Field-mice,  when  artificially  inocu- 
lated, also  sicken ;  among  dogs  only  over-fed 
pet  dogs,  like  pugs,  are  even  relatively  suscept- 
ible ;  goats  seem  to  be  immune.  The  disease 
may  occur  epidemically  among  fowls  and 
pheasants. 

Infection  in  man  is  for  the  most  part  extra- 
uterine,  yet  placental  intra-uterine  infection 
does  sometimes  occur  and  may  manifest  itself 
only  after  birth,  thus  giving  an  appearance  as 


202  BACTERIOLOGY. 

if  the  tubercle  bacteria  themselves  were  in- 
herited. As  a  matter  of  fact  only  the  predisposi- 
tion to  tuberculosis  is  really  inherited.  A. 
Gartner  obtained  eggs  which  contained  tubercle 
bacteria  only  in  the  case  of  intra-abdominal  ex- 
perimental tuberculosis  of  female  canaries. 
The  infection  of  birds'  eggs  corresponds,  how- 
ever, to  a  placental  infection  in  mammals  and 
not  to  the  infection  of  a  mammalian  egg.  The 
conveyance  of  these  bacteria  into  the  ovum  by 
means  of  the  semen  does  not  take  place  ;  but,  in 
cases  of  tuberculosis  of  the  male  sexual  organs 
an  infection  of  the  female  sexual  organs  may 
result  and  a  placental  infection  of  the  foetus 
follow  in  its  track. 

In  the  outside  world  the  bacteria  are  found, 
according  to  Cornet,  only  where  •  sputum  has 
been  deposited  in  great  quantities,  as  in  the 
sick-room,  while  in  the  open  the  sun  soon  de- 
stroys them,  so  that  they  have  been  found  out 
of  doors  only  once,  and  then  (by  Schnirer)  in 
dust  adhering  to  grapes. 

In  leprosy  Armauer  Hansen  discovered  rods 
which  behave  toward  stains  like  the  tubercle 
bacteria,  but  are  somewhat  more  pointed  in 
shape.  They  are  found  with  special  frequency 
in  the  skin,  where  they  are  enclosed  in  large 
cells  (Fig.  25  C),  which  were  earlier  described 
by  Virchow  as  lepra-cells.  Attempts  to  cul- 


DESCRIPTIONS    OF   PATHOGENIC    BACTERIA.    203 

tivate  the  germ  have  not  succeeded.  Arning 
successfully  infected  a  criminal  condemned  to 
death  at  Honolulu,  and  Melcher  and  Ortmann 
seem  once  to  have  obtained  an  infection  in 
rabbits. 

In  syphilis,  Lustgarten  has,  by  staining,  dem- 
onstrated special  rod  bacteria  both  in  primary 
syphilitic  manifestations  and  in  the  inherited 
disease.  This  is  really  the  only  fact  that  sup- 
ports the  view  that  these  bacteria  are  the  cause 
of  syphilis.  Bacteria  occur  in  the  secretion  of 
the  prepuce  which,  in  consequence  of  being 
impregnated  with  fat,  stain  in  a  manner  simi- 
lar to  Lustgarten's  bacteria  ;  the  wax  of  the 
outer  ear  imparts  to  various  bacteria  a  similar 
peculiarity  of  stain. 

It  is  by  no  means  easy  to  distinguish  be- 
tween the  bacteria  of  tuberculosis,  leprosy, 
syphilis  and  smegma  by  methods  of  staining. 
The  tubercle  bacilli,  by  virtue  of  a  mucous- 
like  substance  occurring  in  the  membrane 
(isolated  by  Weyl),  possess  a  remarkable  re- 
sistance to  acids.  Ehrlich  was  the  first  to 
make  use  of  this  property  in  differential  stain- 
ing. If  these  bacteria  are  stained  red  with  a 
mordant  stain,  as  with  carbolic  acid  fuchsin  or 
aniline  water  fuchsin,  the  stain  resists  sub- 
sequent treatment  with  strong  mineral  acids, 
while  other  bacteria  as  well  as  cell-nuclei  are 


204  BACTERIOLOGY.  » 

decolorized.  The  latter  may  then  be  given  a 
contrast  stain  with  a  green  or  blue  dye.  With 
this  treatment  the  red  tubercle  bacilli  stand 
out  in  sharp  relief  against  a  green  or  blue  back- 
ground. The  leprosy  bacteria  when  once 
stained,  behave  in  almost  the  same  manner  but, 
according  to  Baumgarten,  they  differ  from  the 
tubercle  bacteria  in  staining  quickly  and  well 
in  a  simple  watery  solution  of  fuchsin  without 
mordant.  The  syphilis  bacteria  are  easily  de- 
colorized by  mineral  acids,  the  smegma  and  ear- 
wax  bacteria  by  alcohol. 

Actinomycosis  in  man  was  referred  by  B. 
Langenbeck  as  far  back  as  1845  to  the  growth 
of  a  mould,  but  was  first  accurately  described 
by  J.  Israel  in  1878  ;  the  microbes  were  ob- 
tained in  pure  culture  by  Bostro'em,  M.  Wolff 
and  J.  Israel.  Actinomycosis  in  cattle  was  rec- 
ognized in  1877  by  Bollinger,  and  the  disease 
was  communicated  to  calves  by  Ponfick.  When 
bones,  such  as  those  of  the  jaw  or  the  mastoid 
process,  are  attacked  by  the  suppuration  ac- 
companying this  disease  there  are  found  small, 
gritty,  yellowish  granules  which  consist  of  a 
central  core  of  tangled  filaments,  from  which 
club-shaped  rays  shoot  out  peripherally.  The 
threads  are  often  branched  and  have  the  char- 
acter of  true  sheathed  filaments  inside  of 
which  both  rod  and  coccus  forms  are  found. 


DESCRIPTIONS   OF   PATHOGENIC   BACTERIA.     205 

The  various  forms  of  this  germ  that  have  been 
discovered  up  to  the  present  time  are  almost 
the  same  as  those  found  among  tubercle  bac- 
teria. In  cultures  also  the  growth-forms  often 
suggest  those  of  the  tubercle  bacteria  ;  perhaps 
these  organisms  belong  to  one  and  the  same 
genus  of  moulds.  The  ray-fungus  stains  by 
Gram's  method  like  the  bacteria  of  tubercu- 
losis and  leprosy.  In  the  beginning  it  grows 
best  when  the  access  of  air  is  prevented,  but 
soon  adapts  itself  to  aerobic  conditions.  Infec- 
tion has  succeeded  with  rabbits  and  guinea- 
pigs.1  Natural  infection,  it  is  thought,  may 
take  place  through  introduction  of  the  parasite 
into  the  body  upon  grains  of  various  cereals, 
but  I  have  not  succeeded  in  demonstrating 
microscopically  or  culturally  any  one  of  the 
growth  forms  in  a  single  case  that  has  pre- 
sented itself.  Actinomycosis  may  spread  from 
the  jaw  to  the  internal  organs,  lungs,  liver, 
heart  and  brain  ;  perhaps  the  skin  also  may 
be  primarily  affected.  Hofmann  von  Wellen- 
hof  and  Gruber  found  a  bacteria-like  organism 
living  under  saprophytic  conditions  which 

1  The  actinomyces  fungus  discovered  by  Duncker  in  swine  is  dif- 
ferent from  that  occurring  in  cattle  and  from  that  found  in  human 
actinomycosis.  The  microscopic  forms  of  the  cattle  actinomyces  of 
Germany  differ  from  those  shown  by  an  actinomyces  from 
Tasmania  and  the  mainland  of  Australia,  sent  me  by  Archibald  Park 
in  1891. 


206  BACTERIOLOGY. 

behaved  itself  in  experiments  upon  animals 
very  like  the  actinomyces  fungus. 

In  glanders,  LofHer  and  Schiitz  discovered  in 
1882  minute  rods  which  do  not  form  endo- 
spores  and  are  joined  to  one  another  in  short 
threads  ;  according  to  Semmer  branching  is 
occasionally  shown  ;  the  rods  do  not  stain  by 
Gram's  method,  and  in  sections  can  often  be 
perceived  only  with  considerable  difficulty. 
They  grow  only  at  a  temperature  above  22°, 
and  form  moist,  shiny  white  layers  upon  agar 
and  blood  serum  ;  upon  potato  they  develop 
yellow  incrustations,  later  becoming  brown  ; 
virulence  is  very  soon  lost.  The  freshly 
cultivated  bacteria  are  very  virulent  and  the 
disease  is  extremely  contagious,  so  much  so, 
that  already  two  bacteriologists',  ProtopopofT 
and  Hofmann  von  Wellenhof,  have  lost  their 
lives  through  accidental  self-inoculation. 

Men,  horses,  mules  and  asses  are  especially 
susceptible  to  this  germ,  next  stand  goats  and 
cats,  sheep  and  dogs  are  more  resistant,  and 
swine  still  more ;  neat  cattle  are  immune. 
Guinea-pigs  and  field  and  wood  mice  succumb 
readily  to  experimental  inoculation ;  house 
mice  and  white  mice,  on  the  other  hand,  are 
immune.  According  to  Leo,  however,  white 
mice  succumb  if  they  are  made  artificially 
diabetic  by  feeding  with  phloridzin.  Among 


DESCRIPTIONS    OF    PATHOGENIC    BACTERIA.    2O/ 

birds,  only  pigeons  are  susceptible.  Experi- 
mental glanders  in  the  guinea-pig  takes  the 
form  of  an  acute  miliary  tuberculosis  which 
leads  to  death  in  a  few  days. 

The  existence  of  parasites  in  affections  such 
as  the  granulation  tumors  has  not  been  proved 
up  to  this  time  ;  especially  is  this  true  of  car- 
cinoma and  sarcoma.  It  may,  however,  be 
mentioned  that  the  Perlsucht  form  of  tubercu- 
losis was  formerly  considered,  on  the  ground  of 
microscopic  observations,  as  lympho-sarcoma, 
and  rhinoscleroma  was  thought  to  be  a  kind  of 
sarcoma.  Another  form  of  tumor  which  de- 
velops in  the  spermatic  chord  of  the  horse  and 
was  regarded  on  histological  grounds  as  sarcoma 
was  attributed  by  Rivolta  and  Johne  to  the 
invasion  of  bacteria,  the  germ  being  an  asco- 
coccus  or  coccus  arranged  in  rounded  zooglceal 
masses. 

It  is  important  to  bear  in  mind  that  bacteria 
are  not  the  only  organisms  that  can  provoke 
fermentation  and  disease.  We  need  only  re- 
call, in  fact,  the  familiar  case  of  the  alcoholic 
fermentation  which  is  produced  by  the  so- 
called  yeast  plant.  These  yeasts  really  belong 
to  the  group  of  moulds,  whether  we  take  Han- 
sen's  view  that  they  should  be  placed  in  the 
ascospore-forming  genus  Saccharomyces,  or  re- 
gard them  with  Brefeld,  Juhler  and  Jorgensen 


208  BACTERIOLOGY. 

as  developmental  forms  of  different  genera  and 
species  of  moulds.  It  was  demonstrated  some 
time  ago  by  Lewis  that  flagellates  or  cilia- 
bearing  monads  were  sometimes  found  in  the 
blood  of  rats  and,  according  to  Gaule,  Rattig 
and  others,  members  of  this  group  are  found 
also  in  the  blood  of  frogs.  There  undoubtedly 
exist,  therefore,  microbes  belonging  to  the  ani- 
mal kingdom  which  are  capable  of  inducing 
fatal  septicaemia.  Von  Wittich  and  Koch 
found  septicaemic  monads  of  a  like  kind  in  the 
blood  of  German  marmots. 

Loesch  as  far  back  as  1871,  and  subsequently 
Koch,  Kartulis  and  others  demonstrated  the 
presence  of  amoebae  in  the  human  intestine  in 
oases  of  dysentery  and  also  in  the  liver-abscesses 
not  infrequently  accompanying  -this  disease. 
These  amoebae  belong  perhaps  to  the  group  of 
protozoa.  The  successful  communication  of 
the  disease  to  cats  and  dogs  by  inoculation  with 
the  amoebae  makes  it  seem  probable  that  the 
amoebae  are  the  cause  of  the  disease.  In  the  in- 
testinal ulcers  there  are  always  found  bacteria 
as  well,  rod-forms  especially,  probably  the  results 
of  secondary  infection  ;  in  the  liver-abscesses, 
streptococci  and  staphylococci  are  at  times  to  be 
observed  along  with  the  amoebae.  Organisms 
of  a  similar  kind,  which,  to  be  sure,  were  placed 
by  Woronin  among  the  Myxomycetes  or  slime- 


DESCRIPTIONS   OF   PATHOGENIC    BACTERIA.    209 

fungi,  occur  in  a  remarkable  plant  disease, 
the  "  finger  and  toe  disease  "  of  cabbages  ;  Wor- 
onin  called  this  myxamceba,  Plasmodiophora 
brassicce. 

In  some  diseases  of  plants,  bacteria  may  ap- 
pear as  the  exciting  cause,  but  as  a  rule  the 
acid  reaction  of  plant  tissue  hinders  bacterial 
growth.  The  wet-rot  of  potato  is  caused,  ac- 
cording to  Reinke  and  Berthold,  by  an  endo- 
sporous  bacillus  which  penetrates  the  interior 
when  the  cork  layer  is  injured.  According  to 
Wakker,  the  "  yellow"  disease  of  hyacinths  in 
Holland  is  due  to  bacteria  which  occur  in 
yellow  slimy  masses  in  the  vessels  of  the  bulb 
and  in  the  vessels  and  parenchyma  of  the 
leaves.  Ad.  Mayer  considered  the  mosaic 
disease  of  tobacco  leaves  to  be  due  to  bacteria, 
and  Arthur  attributed  a  widely-spread  disease 
of  the  pear-tree  in  America  to  a  species  named 
M.  amylovorus.1 

Among  men  and  domestic  animals  there  are 
some  diseases  caused  by  microbes  belonging 
to  the  group  of  animals,  known  as  Protozoa  ; 
the  taxonomic  position  of  these  organisms  is 
still  in  controversy,  however.  The  disease 
known  as  surra,  a  severe  and  often  fatal 

1  An  excellent  summary  of  the  present  state  of  our  knowledge 
regarding  bacterial  diseases   of  plants  is  given  by  Erwin  F.  Smith, 
in  the  American  Natitralist,  Aug.  1896,  pp.  626  et.  seq. — E.  O.  J. 
14 


2IO  BACTERIOLOGY. 

septicaemia  occurring  in  India  among  horses, 
asses,  and  camels,  is  caused  by  flagellate  monads 
(Crookshank.) 

In  1882,  Laveran  proved  that  animal  mi- 
crobes were  present  in  the  blood  of  patients 
suffering  with  malaria ;  this  microbe  was 
called  Plasmodium  malaria  by  Marchiafava 
and  Celli.  Gerhardt  has  been  able  to  cause 
malaria  in  healthy  men  by  transfusion  of  blood 
containing  these  minute  organisms,  which  are 
certainly  to  be  regarded  as  the  exciting  cause 
of  the  disease.  Attempts  at  cultivation  have 
not  succeeded  up  to  the  present  time,  so  that 
the  course  of  individual  development  must  be 
inferred  from  inspection  of  the  different  forms 
in  various  stages  of  development. 

In  the  smallest  disk-shaped  forms, — which, 
however,  can  change  their  shape  in  an  amoe- 
boid fashion, — the  nucleus  is  large  in  pro- 
portion to  the  cytoplasm ;  in  the  older  indi- 
viduals the  case  is  reversed ;  the  plasm  of  the 
young  forms  is  homogenous,  that  of  the  older 
ones  often  granular.  In  the  older  forms  there 
is  always  found  the  black  malarial  pigment 
which  is  called  melanin  and  is  supposed  to  be 
the  digested  and  altered  haemoglobin.  The 
fully  formed  parasites  develop  flagella  which 
often  break  loose  from  the  cell ;  frequently  the 
flagella  show  knob-shaped  swellings  usually 


DESCRIPTIONS   OF   PATHOGENIC   BACTERIA.     211 

at  the  end.  Some  parasites  occur  in  the  form 
of  crescents  which,  in  blood  removed  from  the 
blood  vessels,  are  slowly  altered  to  spindle- 
shaped,  oval,  and  finally  spherical  structures  ; 
;t  is  still  uncertain  whether  this  transformation 
takes  place  also  in  the  circulating  blood. 
While  the  spores  are  being  formed,  the  pigment 
gathers  at  the  centre.  The  protoplasm  then 
falls  apart  by  radial  striations  into  a  rosette- 
shaped  figure  ;  the  peripheral  portions  of  this 
become  the  spores,  the  central  heap  of  pigment 
remaining  behind.  The  spores  arise,  there- 
fore, by  a  kind  of  segmentation  of  the  cell- 
contents.  The  unpigmented  spore  remains 
free  in  the  blood  for  some  time,  then  attaches 
itself  to  a  red  blood-corpuscle  which  it  pen- 
etrates and  then  proceeds  to  nourish  itself  at 
the  expense  of  the  haemoglobin  of  the  cor- 
puscle. The  crescents,  according  to  Laveran, 
are  the  encysted  form  of  the  parasite ;  accord- 
ing to  Mannaberg,  however,  they  are  a  con- 
jugation-body or  syzygy,  that  is  to  say,  an  in- 
complete fusion  of  two  parasites  ;  on  this  inter- 
pretation, conjugation  would  be  a  preparation 
for  sporulation. 

Two  views  prevail  as  to  the  relation  of  these 
forms  to  the  different  kinds  of  malarial  fever. 
Golgi  assumes  the  existence  of  three  varieties 
of  the  parasite  (namely,  a  quartan,  a  tertian, 


212  BACTERIOLOGY. 

and  a  quotidian  parasite),  each  one  of  which 
produces  different  forms  of  the  fever  in  accord- 
ance with  the  peculiarities  of  its  development. 
Marchiafava  would  add  to  these  yet  a  fourth, 
the  malignant  tertian  parasite.  This  belief  in 
the  existence  of  several  parasites  corresponds 
to  the  usage  of  physicians  and  has  therefore 
found  wide  acceptance.  But  it  must  still  be 
considered  as  an  open  question  whether  the 
evidence  for  the  existence  of  these  varieties  is 
altogether  conclusive.  Such  progress  as  has 
been  made  in  bacteriology  should  incline  us  to 
use  great  caution  about  accepting  any  attempt 
at  schematic  division.  Laveran  in  fact  still 
maintains  the  other  view  ;  according  to  him 
there  is  only  one  pleomorphic  parasite  and  the 
different  kinds  of  fever  are  due  riot  to  different 
varieties  or  species  of  the  parasite  but  to  the 
varying  dispositions  of  men.  This  view  has 
the  great  merit  of  being  more  in  harmony  with 
the  progress  of  micro-parasitology. 

Since  it  has  been  shown  that  the  so-called 
tubercle  bacilli  are  parasitic  growth-forms 
of  a  mould,  I  may,  in  conclusion,  add  some 
remarks  upon  the  diseases  of  men  and  animals 
due  to  moulds.  The  true  moulds  are  aerobic 
and  capable  of  forming  spores  only  with  ac- 
cess of  air,  while  the  mycelium  and  the 
torula  forms  are  able  to  develop  when  air 


DESCRIPTIONS   OF   PATHOGENIC   BACTERIA.     213 

is  shut  off.  We  usually  find  moulds  there- 
fore, parasitic  only  upon  the  surface  of  the 
body, — upon  the  skin  or  the  mucous  mem- 
branes. The  favus  mould  was  identified  by 
Schonlein  as  far  back  as  1839  as  the  cause  °f 
scald,  and  was  named  in  honor  of  its  discoverer 
Achorion  Schbnleinii ;  the  different  kinds  of 
favus  occurring  in  man  may  be  only  varieties 
of  one  species.  The  very  similar  Trichophyton 
tonsurans,  which  was  found  in  1845  by  Gruby 
and  Malmsten,  is  certainly  another  species. 
The  cause  of  the  disease  pityriasis  versicolor 
was  discovered  by  Eichstedt  in  1846  to  be  the 
Microsporon  furfur. 

The  disease  known  as  thrush,  an  affection  of 
the  mucous  membrane,  is  caused  by  Oidium 
albicans ;  it  occurs  often  among  children, 
especially  upon  the  mucous  membrane  of  the 
mouth,  while  in  adults  it  can  develop  only  in 
specially  weakened  conditions  such  as  those 
brought  about  by  typhoid  fever  or  phthisis. 
The  torula  form  may  also  grow  and  germinate 
in  the  interior  of  the  body.  When  rabbits  are 
inoculated  intravenously,  a  general  mycosis  of 
the  internal  organs  is  brought  about.  In  man, 
a  case  is  recorded  by  Wagner  in  which  the 
oidium  made  its  way  into  an  injured  vein  and 
from  there  into  the  brain,  where  it  gave  rise  to 
a  fatal  mycosis. 


214  BACTERIOLOGY. 

The  true  moulds  have  been  observed  grow- 
ing spontaneously  upon  the  cornea,  in  the 
passage  of  the  outer  ear,  upon  the  mucous 
membrane  of  the  larynx  and  in  the  lungs  ;  in 
these  places  they  can  also  form  spores.  The 
internal  organs  to  which  the  germs  must  be 
conveyed  by  means  of  the  blood  vessels  are 
rarely  affected  by  moulds,  since  the  moulds  as 
a  rule  grow  only  superficially.  On  the  other 
hand  it  is  easy  to  cause  infection  of  the  in- 
ternal organs  of  the  lower  animals  with  moulds 
by  injecting  spores  into  their  circulation  ;  but 
new  spore-formation  never  occurs  under  these 
conditions.  There  is,  so  far  as  I  know,  only  one 
instance  where  an  infection  of  man  has  taken 
place  by  way  of  the  intestine.  In  one  species 
of  Mucor  a  form  and  arrangement  of  the  my- 
celial  threads  occurs  which  recalls  very  strik- 
ingly the  ray-fungus.  It  is  a  most  remarkable 
thing  that  these  disease-producing  moulds, 
like  Aspergillusfumigatus  2J&&flavescens, Mucor 
rhizopodiformis  and  corymbifer,  although  not 
usually  able  to  act  pathogenically,  and  gen- 
erally unable  to  adapt  themselves  to  a  parasitic 
existence,  are  yet  sometimes  able  to  enter  im- 
mediately upon  the  production  of  disease  on 
the  sole  capital  of  characters  acquired  through 
a  saprophytic  habit  of  life.  This  striking  ex- 
ample shows  that  pathogenic  bacteria  must 


DESCRIPTIONS   OF   PATHOGENIC   BACTERIA.     215 

be  carefully  studied  in  their  relations  to  their 
saprophytic  adaptations,  if  we  do  not  wish  to 
embrace  ideas  which  have  indeed  the  merit  of 
being  convenient  to  physicians  but  are  in 
other  respects  wide  of  the  truth. 

[I  have  thought  it  of  interest  to  give  a  brief  resume  of  Sanarelli's 
recent  papers  upon  yellow  fever.1 

The  most  important  study  of  yellow  fever  that  appeared  before 
Sanarelli's  investigations  were  undertaken  was  that  made  in  1888-9 
by  Dr.  Sternberg,  whose  researches  led  to  an  essentially  negative 
result.  Sanarelli,  in  7  out  of  12  autopsies  made  upon  the  bodies  of 
victims  of  yellow  fever  found  a  specific  bacillus  (B.  icteroides]  which 
he  regards  as  hitherto  undescribed.  The  reasons  assigned  for  the 
failure  of  himself  and  others  to  isolate  this  microbe  in  all  cases  of 
yellow  fever  are  :  i.  That  B.  icteroides  multiplies  in  the  human  body 
only  to  a  limited  extent,  the  complete  and  characteristic  effects  of 
the  disease  being  produced  by  only  a  very  small  quantity  of  toxin. 
2.  That  this  toxin,  whether  directly  or  indirectly,  facilitates  to  a  re- 
markable degree  secondary  infections  of  all  kinds.  These  secondary 
infections  with  the  colon  bacillus,  streptococcus,  staphylococcus, 
etc.,  may  of  themselves  be  fatal  to  the  patient,  and  Sanarelli  be- 
lieves that  the  fatal  termination  of  several  cases  observed  by  him  is 
to  be  explained  in  this  way.  3.  That  these  mixed  infections  not  only 
lead  to  the  speedy  disappearance  of  the  specific  microbe,  but  also 
frequently  end  by  transforming  the  organism  of  the  patient  into  a. 
culture  medium  for  almost  all  kinds  of  intestinal  bacteria. 

The  bacteriological  complications  arising  from  these  facts  enhance 
considerably  the  technical  difficulties  of  isolating  the  specific  bacil- 
lus. Sanarelli  did  not  succeed  in  finding  the  germ  in  the  gastro-in- 
testinal  contents  and  is  inclined  to  doubt  if  it  usually  occurs  thereat 
all ;  he  did,  however,  discover  it  in  the  circulating  blood  and  in  some 
of  the  important  organs  of  the  body,  notably  in  the  liver.  He  re- 
fers to  the  prevailing  belief  that  the  infectious  material  in  yellow 
fever  is  localized  in  the  stomach  and  is  to  be  sought  for  especially  in 
the  black  vomit,  but  prefers,  for  his  part,  to  regard  the  gastric  dis- 
turbances as  due  to  the  selective  action  of  the  toxin,  a  view  similar, 
it  will  be  remembered,  to  his  interpretation  of  the  intestinal  lesions 
of  typhoid  fever. 

1  Annales  de  1'Inst.  Pasteur,  June,  Sept.,  Oct.,  1897. 


2l6  BACTERIOLOGY. 

Bacillus  icteroides  grows  readily  upon  the  ordinary  nutritive  media 
fluid  and  solid.  It  is  described  as  a  rod  about  2^-4^  in  length,  with 
rounded  ends,  often  joined  in  pairs,  and  staining  readily  with  the 
ordinary  aniline  dyes,  but  decolorized  by  Gram's  method.  The 
colonies  upon  a  gelatin  plate  resemble  in  some  particulars  those  of 
the  colon  bacillus,  but  never  show  any  trace  of  the  chestnut  color 
developed  in  cultures  of  the  latter ;  so-called  pleomorphism  of  the 
colonies  is,  however,  marked. 

Contrary  to  what  is  true  of  -most  of  the  known  pathogenic  mi- 
crobes, the  growth  of  B.  icteroides  upon  agar  is  especially  character- 
istic and  furnishes  a  diagnostic  test  of  the  first  importance.  If  the 
cultures  are  allowed  to  develop  in  the  incubator  at  37°  for  from  12 
to  24  hours,  and  are  then  transferred  to  a  temperature  of  from  20° 
to  28°,  there  is  produced  what  Sanarelli  regards  as  a  highly  charac- 
teristic appearance.  The  growth  at  the  lower  temperature  forms  a 
sort  of  halo  around  the  portion  of  the  colony  developed  in  the  incu- 
bator, and  this  appearance  is  so  singular  that  according  to  Sanarelli 
a  mere  superficial  inspection  suffices  to  distinguish  immediately,  and 
with  the  naked  eye,  a  colony  of  B.  icteroides  in  the  midst  of  all  other 
bacterial  colonies  yet  described.  As  the  growth  goes  on,  an  effect 
is  produced  as  if  a  layer  of  opaque  paraffin  had  been  poured  over  the 
agar  and  then  impressions  made  in  it  with  a  small  circular  seal,  the 
imprints  of  this  seal  corresponding  with  the  original  transparent 
colonies  grown  in  the  incubator.  The  final  aspect  of  the  culture  is 
compared  to  a  miniature  archipelago  in  which  the  islets  would  be 
represented  by  the  colonies  first  developed,  and  the  surface  of  the 
water  by  the  layer  subsequently  formed  at  the  lower  temperature. 

Blood-serum  and  potato  proved  themselves  to  be  rather  unsuit- 
able media  for  B.  icteroides.  In  milk  the  germ  grows  readily,  but 
without  producing  coagulation.  The  most  favorable  fluid  medium 
tejsted  by  Sanarelli  was  beef  broth  containing  lactose  and  calcium 
carbonate. 

The  germ  is  pathogenic  for  most  of  the  domestic  animals.  Mice, 
guinea-pigs  and  rabbits  succumb  readily  to  inoculation  with  a  pure 
culture.  -The  rabbit  is  considered  as  the  most  favorable  subject  for 
experimental  inoculation,  and  possesses  notable  advantages  over  the 
guinea-pig  both  in  susceptibility  and  in  the  regularity  and  constancy 
of  symptoms  and  death.  The  dog,  however,  presents  the  most  in- 
structive instance  of  close  analogy  with  yellow  fever  as  manifested  in 
man.  Both  in  the  symptoms  and  in  the  anatomical  lesions  Sanarelli 
was  able  to  trace  a  correspondence  at  once  constant  and  precise. 
As  is  the  case  in  man,  the  liver  and  the  kidneys  are  the  organs  es- 


DESCRIPTIONS    OF   PATHOGENIC    BACTERIA. 

pecially  attacked  ;  secondary  infections  with  the  streptococcus  and 
colon  bacillus  sometimes  occur. 

In  the  second  memoir  Sanarelli  details  the  results  of  his  experi- 
ments with  the  yellow  fever  toxin.  Cultures  of  the  germ  15-20  days 
old,  made  in  ordinary  peptonized  meat  broth  and  filtered  through  a 
Pasteur-Chamberland  tube,  afforded  him  a  potent  toxin.  The  toxin 
thus  prepared,  when  injected  into  the  bodies  of  susceptible  animals, 
produced  substantially  the  same  symptoms  as  inoculation  with  the 
specific  bacillus.  In  the  dog,  particularly,  inoculation  with  the 
germ-free  toxin  set  in  motion  the  same  train  of  specific  symptoms 
and  caused  the  same  pathological  changes  in  the  tissues.  "The 
toxin  of  yellow  fever  is  an  exceedingly  powerful  cellular  poison  com- 
parable solely,  in  some  points,  to  the  diphtheria  toxin.  Its  contact 
with  the  tissue  elements  of  the  animal  organism,  especially  the  higher 
species,  determines,  like  that  of  the  diphtheria  toxin,  a  violent  irrita- 
tion, followed  by  retrogressive  processes  which  always  end  in  the 
necrosis  and  fatty  degeneration  of  the  protoplasm." 

Some  very  interesting  experiments  bearing  on  the  question  of 
mixed  infection  are  next  described.  When  B.  icteroides  is  sown 
upon  culture  media  on  which,  the  colon  bacillus,  streptococcus  and 
proteus  respectively,  have  been  previously  grown,  it  is  found  that 
the  growth  of  the  former  is  distinctly  inhibited  by  the  presence  of  the 
soluble  products  of  the  other  microbes.  The  latter,  on  the  contrary, 
grow  excellently  in  a  medium  previously  inhabited  by  B.  icteroides, 
and  are  only  slightly  incommoded  by  the  presence  of  the  soluble 
products  of  one  another,  the  products  of  the  proteus  bacillus  seem- 
ing most  injurious  to  all  concerned.  A  similar  result  was  revealed 
by  a  study  of  the  '  vital  antagonism  '  of  B.  icUroidesvaA  the  microbes 
concerned  in  the  secondary  infections.  Both  Streptococcus  pyog,  and 
Staphylococcus pyog.  an.  speedily  gain  the  upper  hand  over  B.  icter- 
oides, and  a  similar,  though  less  marked  superiority,  is  manifested  by 
the  colon  bacillus.  These  facts  certainly  shed  much  light  on  the 
difficulty  of  demonstrating  the  presence  of  the  yellow  fever  germ  in 
the  bodils  of  victims  of  the  disease,  and  go  far  to  explain  the  nega- 
tive result  reached  by  many  observers. 

In  an  attempt  to  account  for  the  important  part  played  by  mari- 
time commerce  in  the  diffusion  of  yellow  fever,  Sanarelli  records 
a  curiously  significant  observation.  It  was  noticed  that  gelatin 
plates  sown  with  B.  icteroides  sometimes  remained  without  develop- 
ment, although  agar  plates  sown  at  the  same  time  evinced  abundant 
growth.  But  if  a  colony  of  mould  made  its  appearance  on  the 
gelatin  plate,  colonies  of  B.  icteroides  immediately  sprang  up  around 


2l8  BACTERIOLOGY. 

it.  After  some  days  the  colonies  of  B.  icteroides  form  a  sort  of  con- 
stellation around  the  mould,  the  most  abundant  development  taking 
place  in  the  immediate  neighborhood  of  the  latter.  This  observa- 
tion was  experimentally  verified  with  six  species  of  moulds  (not 
named)  "  accidentally  isolated  "  in  the  laboratory,  all  of  which  proved, 
although  in  different  degrees,  capable  of  favoring  the  revivification 
.and  multiplication  of  the  yellow  fever  germ.  To  this  singular 
symbiotic  relation  Sanarelli  is  inclined  to  attribute  the  ready  domi- 
ciling of  the  disease  on  shipboard  and  its  connection  with  warmth, 
moisture  and  darkness,  conditions  which,  by  directly  favoring  the 
germination  of  moulds,  indirectly  favor  B.  icteroides. 

In  some  brief  notes  upon  the  resistance  of  the  germ  to  physical 
and  chemical  agents  it  is  stated  that,  by  exposure  of  broth  cultures 
to  55°,  the  germ  is  killed  in  about  twenty  minutes,  and  that  it  is  in- 
stantly destroyed  by  a  temperature  of  65°.  Dry  heat  at  i  io°-i25°  is 
speedily  fatal,  and  exposure  for  one  hour  aud  ten  minutes  at  100° 
also  suffices  to  destroy  vitality.  Considerable  resistance  is  shown  to 
desiccation,  a  result  of  evident  practical  importance.  In  sea  water 
the  bacillus  shows  great  vitality,  surviving  in  the  sterilized  brackish 
water  of  the  La  Plata  for  upwards  of  ninety  days. 

Sanarelli's  third  memoir  is  devoted  to  a  consideration  of  immunity 
and  serum  therapy.  The  serum  obtained  from  the  bodies  of  yellow 
fever  victims  causes  agglutination  of  B.  icteroides,  although  the  in- 
tensity of  the  reaction  is  said  to  be  quite  variable.  t  This  serum  does 
not  exert  any  protective  power  in  inoculated  animals.  Serum  from 
a  convalescent  provoked  a  tardy  agglutination  and  manifested  a 
slight  preventive  power. 

An  attack  of  yellow  fever  in  man  confers  some  degree  of  im- 
munity against  a  second  attack,  and  hence  it  would  seem  as  if  it 
might  be  possible  in  some  way  to  vaccinate  animals  against  the 
disease.  Attempts  to  produce  immunity  in  the  rabbit  failed  on  ac- 
count of  the  excessive  sensibility  of  this  animal  to  the  yellow  fever 
virus,  and  the  same  difficulty  prevented  the  use  of  the  goat  and  the 
sheep.  The  work  upon  immunization  was  mainly  limited,  therefore, 
to  experiments  upon  the  guinea-pig,  the  dog  and  the  horse.  In  all 
these  animals  immunization  is  an  unusually  difficult  and  laborious 
task.  While  it  is  possible  to  immunize  a  guinea-pig  against  cholera 
or  typhoid  fever  in  from  two  to  three  months,  it  needs  six  to  seven 
months  of  assiduous  and  delicate  work  to  vaccinate  this  animal 
against  yellow  fever.  Dogs  may  be  immunized  somewhat  more 
readily,  but  never  become  tolerant  of  large  doses  of  toxin.  Horses 
are  treated  first  with  small  doses  (5-10  c.c.)  of  a  filtered  culture  of  the 


DESCRIPTIONS   OF   PATHOGENIC   BACTERIA.    2 19 

germ  injected  subcutaneously,  followed  with  intravenous  injections. 
After  two  months  of  treatment  with  filtered  cultures  the  more 
potent  doses  of  cultures  sterilized  by  ether  may  be  used ;  it  is  not 
until  five  to  six  months  after  the  beginning  of  the  treatment  that  the 
first  injection  of  a  living  culture  may  be  safely  hazarded.  During 
this  process  of  immunization  many  of  the  animals  die  and  all  are 
profoundly  affected. 

The  serum  of  animals  immunized  in  this  way  is  endowed  with  pro- 
tective and  curative  properties  and  can  be  used  with  success  in 
animal  experiments.  A  single  instance  may  serve  to  illustrate  the 
results  obtained  by  this  procedure.  A  horse  under  treatment  for  the 
space  of  nine  months  received  subcutaneously  during  this  period 
29c.c.  of  filtered  cultures  and  350  c.c.  of  cultures  sterilized  with  ether, 
and  intravenously  2640  c.c.  of  sterilized  cultures,  345C.C.  of  living  broth 
cultures  and  19  c.c.  of  an  agar  culture.  The  serum  (0.5  c.c.)  from  this 
animal,  when  injected  into  a  guinea-pig  24  hours  before  inoculation 
with  several  times  the  fatal  dose,  conferred  immunity ;  2c.c.  proved 
potent  enough  to  save  the  lives  of  guinea-pigs  when  injected  48 
hours  after  inoculation. — E.  O.  J.] 


CHAPTER  IV. 

THE   CAUSE   OF   INFECTIOUS   DISEASE. 

THE  wish  "  to  know  the  cause  of  things  "  is 
as  old  as  mankind  itself.  In  medicine  the 
scientific  period  may  be  said  to  dawn  at  the 
moment  when  the  question  as  to  the  connection 
of  disease  with  environment  was  clearly  pro- 
pounded by  Diodorus  and  by  Hippocrates,  "  the 
father  of  medicine." 

In  former  times  men  were  generally  satisfied, 
and  they  are  frequently  satisfied  to-day,  with 
the  vaguest  conceptions  of  things,,  conceptions 
based  on  the  common  ground  of  a  search  after 
animate  causes  or  personifications.  Universal 
knowledge  is  plainly  unattainable  in  any  given 
section  of  time  ;  hence  men  have  always  been 
forced  to  piece  out  in  imagination  part  of  the 
lacking  facts, — that  is  to  theorize ;  and  the 
form  such  speculation  assumes  is  naturally  in 
accordance  with  the  measure  of  cultivation 
prevailing  at  the  time.  Even  now,  as  is  clearly 
shown  by  the  conceptions  of  image-worship 
among  both  the  educated  and  uneducated  there 
weighs  upon  wide  strata  of  society  an  impera- 


220 


THE   CAUSE   OF   INFECTIOUS   DISEASE.         221 

tive  necessity  for  personification,  for  animate 
cause.  Men  abandon  the  idea  of  such  animate 
causes  only  after  more  profound  thought  and 
arrive  first  at  a  mechanical,  then  at  a  monistic 
conception  of  the  universe.  Guided  by  the 
pervasive,  all-embracing  law  of  the  conserva- 
tion of  energy,  the  exact  sciences  have  every- 
where struggled  through  to  a  mechanical,  and 
in  part  even  to  a  monistic  standpoint.  The 
extraordinary  complexity  of  the  phenomena 
which  confront  us  in  the  consideration  of  the 
origin  of  disease  doubtless  accounts  for  the 
fact  that  up  to  this  time  no  one  of  the  concep- 
tions in  medical  theory, — either  the  dominant 
ones  or  those  in  direct  conflict  with  them, — 
have  been  freed  altogether  from  the  old  mys- 
tical animism.  For  this  very  reason  not  only 
do  scientific  periodicals  resound  daily  with  the 
clash  of  antagonistic  principles,  but  the  conflict 
is  continued  in  the  daily  press  and  even  in  the 
conversations  on  street  corners. 

In  the  presence  of  the  great  pestilence  which 
the  Greeks  before  Troy  T  ascribed  to  the  arrows 
of  the  offended  god  Apollo,  Homer  makes  the 
father  of  gods  and  men  say : 

"  Lo,  how  men  blame  the  gods  !  From  us  they  say, 
spring  troubles.  But,  through  their  own  perversity,  and 
more  than  is  their  due,  they  meet  with  sorrow." 

1  The  passage  in  question  occurs  in  the  Odyssey  I.,32-34 — E.  O.  J. 


222  BACTERIOLOGY. 

This  notion  that  pestilences  are  punishments 
for  sins,  and  that  they  can  be  combated  by 
sacrifices,  prayers,  and  pilgrimages,  survives 
to-day  in  the  midst  of  civilized  Europe,  an  exam- 
ple of  the  deep-rooted  proclivity  in  untrained 
minds  towards  a  search  after  the  animate,  to- 
wards ontological  speculation.  The  conveni- 
ence of  this  ontological  conception  has  given  to 
the  bacteria,  as  if  in  pure  mockery  of  all  scien- 
tific thought,  an  opportunity  to  celebrate  their 
resurrection  as  the  true  disease-entities.  Now, 
indeed,  every  sewing-girl  knows  that  these 
good-for-nothing  bacteria  are  the  cause  of 
"  fevers."  Given  the  specific  germ  and  the 
supposition  is  that  we  know  everything  need- 
ful ;  methods  of  fighting  the  disease,  of  disin- 
fection and  of  healing  are  mere  unimportant 
details.  We  cannot  enough  scorn  those  older 
physicians  who  knew  nothing  about  bacteria, 
but  who  could  not  bring  it  into  harmony  with 
their  better  philosophic  schooling  that  these 
things  should  be  suddenly  presented  to' them 
in  pure  cultures  and  in  beautifully  colored  mi- 
croscopic preparations,  as  the  cause  of  disease. 
But  in  truth  a  sound  kernel  lay  in  their  crit- 
icism. It  was  in  a  kindred  spirit  that  Liebig 
ridiculed  Pasteur,  remarking  a  propos  of  Pas- 
teur's statement  that  the  yeasts  were  the  cause 
of  alcoholic  fermentation,  that  one  could  not  see 


THE   CAUSE   OF   INFECTIOUS   DISEASE.         223 

causes.  Physicians,  however,  were  not  embar- 
rassed by  such  considerations  and,  under  the 
influence  of  Koch's  ingenious  methods,  it  be- 
came a  pastime  to  show  the  causes  of  disease 
in  pure  cultures ;  the  amusement  flourished 
even  in  the  drawing-room,  and  the  phraseology 
of  the  new  game  became  popular  everywhere. 
We  shall  probably  best  reach  a  scientific 
understanding  of  the  significance  of  bacteria  in 
the  origination  of  disease  if  we  consider  briefly 
the  chief  ideas  hitherto  held  concerning  disease. 
The  conception,  now  generally  embraced,  of  a 
"  specific  infectious  disease "  presents  itself 
first  in  the  writings  of  the  great  English  phy- 
sician, Sydenham.  By  this  term  is  understood 
a  sharply  defined  characteristic  malady  which, 
in  uncomplicated  and  "  typical  "  cases,  is  clear- 
ly distinguishable  in  its  course  and  symptoms 
from  other  diseases  ;  measles,  smallpox,  scarlet 
fever,  malaria,  pneumonia,  and  cholera  are  such 
"  specific  infectious  diseases."  It  was  precisely 
this  individuality  of  the  "  typical  "  cases  that 
pointed  to  an  individuality  of  origin,  and  in 
exactly  this  general  sense  Sydenham  first  com- 
pared "  species  of  disease  "  with  species  of  plants. 
In  the  eyes  of  this  physician,  therefore,  the 
"  specific  "  disease  itself  was  an  "  entity,"  it  was 
personified.  To  have  done  away  with  this  con- 
ception is  one  of  the  great  services  of  Lotze 


224  BACTERIOLOGY. 

and  Virchow,  who  recognized  more  clearly 
than  their  predecessors  that  disease,  as  well  as 
normal  life,  is  a  process.  A  process,  a  me- 
chanical or  dynamical  process,  cannot,  how- 
ever, be  a  living  entity ;  and  hence  Lotze  and 
Virchow  struck  a  fatal  blow  at  the  unscientific 
notion  of  a  disease  essence.  Something  in 
addition  to  this  notion,  however,  dwelt  in  the 
conception  of  Sydenham,  namely  the  observa- 
tion that  the  "  specific  "  disease  must  have  a 
cause,  although  he  did  not  separate  sufficiently 
the  conception  of  a  predisposition  to  disease 
from  that  of  the  cause  of  disease.  He  recog- 
nized further  that  the  character  of  the  specific 
infectious  disease  varies  greatly  in  different 
epidemics,  and  attributed  this  variation  to  the 
genius  epidemicus,  without  remarking  that  the 
term  expressed  a  fundamental  departure  from 
his  conception  of  rigid  disease  types. 

From  the  manifest  opposition  between  Syd- 
enham's  conception  of  a  "  disease  species  "  as 
an  entity,  and  Lotze  and  Virchow's  conception 
of  disease  as  a  process,  we  are  able  at  once  to 
understand  Virchow's  direct  and  vigorous  op- 
position to  those  bacteriologists  who  still  stick 
fast  in  the  fetters  of  ontology,  and  for  whom 
disease-producing  bacteria  are  only  mystical 
entities  which  they  would  like  to  set  in  the 
place  of  the  older  personifications  of  priestcraft 


THE   CAUSE    OF   INFECTIOUS   DISEASE.         22$ 

to  be  worshipped  by  devout  physicians  and 
laity. 

Virchow,  following  up  the  process  of  dis- 
ease as  far  as  possible,  came  at  last  upon  the 
diseased  cells.  Here  he  too  fell  into  a  singular 
error.  He  set  up  the  diseased  cell  as  the  es- 
sence of  disease,  thereby  substituting  another 
entity  for  the  one  he  had  just  thrown  down. 
It  was  a  weak  place  in  the  cellular  pathology 
and  one  which  Virchow's  opponents  were  of 
course  quick  to  attack,  without,  however,  giv- 
ing due  consideration  to  one  point  in  his  theory, 
namely,  that  he  did  not  lose  sight  of  the  dis- 
ease process  in  his  contemplation  of  the  dis- 
eased cells  as  the  microscopic  disease  entities. 
He  rightly  conjectured  that  the  something  that 
appeared  as  disease  must  be  something  that 
was  already  preformed  in  the  normal  organism. 
As  the  cause  is  essential  to  its  effect,  so  the 
production  of  disease  requires  an  inward  pre- 
disposition. Lotze  had  already  expressed 
himself  in  a  similar  way. 

In  regard  to  the  normal  processes  of  life  the 
same  principle  had  been  established  for  a  long 
time  through  the  investigations  of  the  German 
physiologists  Haller,  Reil  and  Johannes  Miiller. 
Whatever  be  the  outside  forces  that  act,  the 
eye  perceives  only  light,  and  the  ear  only  sound; 
the  glands  simply  secrete  and  the  muscles  con- 


226  BACTERIOLOGY. 

tract.     It  is  therefore  the  internal  condition  of 
the  organism,  of  its  organs,  tissues  or  cells,  that 
alone  determines   the   character   of  the  effect. 
The   impulse  that   must    come    from    outside 
to  produce  these  effects  is  called  the  stimulus. 
Hence  there  must  exist  a  fundamental  internal 
organization,  that  is  to  say,  a  predisposition  to 
something  external.       Since   also  the  physio- 
logical manifestations  remain  the  same,  while 
the  character  of  the   stimulus  varies,  the  true 
cause  of  the  manifestations  must  lie  in  this  in- 
ternal organization.     The  intrinsic   predispo- 
sition is  physiologically  the  true  and  sufficient 
cause,  and  therefore  the  sole  cause  of  the  nor- 
mal processes  of  life.     On  this  side  Virchow 
and  Brown  indeed  recognized  the  fact  that  a 
quantitative  excess  in  a  normal  stimulus  may 
be  the  cause  of  disease ;  too  much  light,  for 
example,  produces  blindness.     The  effect  of  a 
stimulus  may  likewise  be  too  great  if  the  natu- 
ral predisposition  of  the  organism  be  too  feeble, 
although   the    stimulus    itself  is    still  within 
physiological    limits   for  a  normal  organism. 
Disease,  then,  may  be  regarded  as  the  effect 
produced  by  quantitative  changes   in  normal 
conditions,  either  when  the  physiological  organ- 
ization is  too  feeble  or  the  stimulus  too  intense. 
Apparently,  at  least,  infectious  diseases  which 
were  presumed  to  introduce  an  entirely  new 


THE   CAUSE    OF   INFECTIOUS   DISEASE.         22J 

qualitative  element  scarcely  fitted  into  this 
conception.  The  doctrine  of  the  causation  of 
infectious  diseases  is  accordingly  not  indebted 
to  Virchow  for  its  furtherance  nearly  so  much 
as  are  other  realms  of  pathology. 

On  the  other  side,  those  investigators  who 
were  dissatisfied  with  Virchow's  explanation 
fell  into  the  opposite  error  in  their  own  inves- 
tigations. The  Viennese  doctor  Plenciz  had 
expounded  very  clearly  and  more  fully  than 
any  one  had  done  before  him  the  doctrine  that 
the  cause  of  disease  must  be  sought  in  the  ex- 
istence and  activities  of  minute,  specific  living 
things.  Afterwards  Eisenmann  and  still  more 
acutely  Henle  set  forth  this  parasitic  theory 
of  infectious  diseases,  which  grew  then  steadily 
stronger  through  the  added  force  of  important 
discoveries.  In  our  own  time,  through  the 
work  of  Davaine,  Pasteur,  Klebs,  F.  Cohn,  J. 
Schroter,  and  Koch,  it  has  become  the  prevail- 
ing theory.  By  his  statement  of  this  theory 
Henle  was  thrown  into  just  as  sharp  opposition 
to  Virchow  as  Koch  has  been  recently,  and  at 
that  time  was  forced  by  Virchow's  want  of  con- 
sideration into  other  lines  of  activity,  a  fact  that 
enables  us  to  understand  many  personalities  in 
current  controversy. 

The  now  well-established  parasitic  theory 
of  disease  asserts  that  every  "  specific  "  infec- 


228  BACTERIOLOGY. 

tious  disease  is  caused  by  a  "  specifically " 
characteristic  small  living  thing  or  mi- 
crobe. Most  of  these  microbes — but  not  all — 
belong  to  the  group  of  bacteria.  These  bac- 
teria, which  are  Jrherefore  entities  altogether 
external,  are,  as  Koch  has  set  forth  with  great 
clearness,  the  sole  true  and  sufficient  cause  of 
the  infectious  diseases.  Differences  in  these  dis- 
eases are  due  to  differences  in  the  small  living 
things  at  the  bottom  of  the  process,  in  the  dis- 
ease-producing bacteria  alone.  In  short,  bac- 
teria constitute  the  "  entities  "  of  infectious 
disease.  According  to  the  theatrum  diabolo- 
rum,  the  view  prevailed  in  the  Middle  Ages 
that  "  every  sin  is  under  the  control  of  and 
operated  by  a  particular  devil  "  ;  at  present 
each  disease  in  similar  fashion  'has  its  own 
devil  in  the  form  of  a  specific  bacilliis.  Beelze- 
bub, the  god  of  invisible  evil  flies,  is  peculiarly 
the  protecting  patron  of  the  "  specific  "  bacteri- 
ologists. 

'  Between  this  conception — a  matter  in  which 
the  French  daily  press  finds  its  oracle  in  Pas- 
teur and  the  German  in  Koch — and  the  con- 
ception of  Virchow,  there  exists  a  profound 
antagonism.  It  is  the  same  conflict  that  pre- 
vailed between  Liebig  and  Pasteur  over  the 
physiology  of  fermentation.  Liebig  sought 
the  cause  of  fermentation,  as  Virchow  did  that 


THE   CAUSE    OF   INFECTIOUS   DISEASE.         22Q 

of  disease,  in  the  internal  constitution  of 
the  fermentable  substances,  while  Pasteur  con- 
ceived the  cause  to  be  the  external  and  visible 
yeast-cells.  This  conflict  of  opinion  is  now 
still  further  complicated  by  Pettenkofer's  theory 
that,  at  least  for  certain  diseases  such  as 
typhoid  fever  and  cholera,  the  determining 
cause  or  essence  is  to  be  found  in  the  external 
conditions  which  vary  according  to  time  and 
place.  Here  we  have  put  forth  as  the  true 
and  sufficient  cause  of  epidemic  disease  three 
wholly  dissimilar  things,  upheld  by  three  dif- 
ferent schools,  and  which  are  all  treated  as 
"  entities  "  or  personifications.  Virchow  finds 
an  internal  cause  in  the  diseased  cells,  his  op- 
ponents see  an  external  cause  in  the  germs 
that  bring  about  disease,  and  Pettenkofer  sees 
a  cause  in  those  external  conditions  which 
play  no  particular  role  either  in  the  eyes  of. 
Virchow  or  in  those  of  Virchow's  chief  oppo- 
nents. At  the  same  time,  however,  it  must  be 
said  that  Virchow  consistently  attempts  to 
break  free  from  the  personification  idea  and 
to  arrive  at  some  conception  based  on  the 
comprehension  of  processes. 

I  shall  now  attempt  to  show  what  is  false  in 
each  of  these  conceptions  and  what  is  scien- 
tifically tenable,  and  in  so  doing  I  shall  point 
out  that  all  these  investigators  recognized  a 


230  ,     BACTERIOLOGY. 

part  of  the  truth,  but  that  no  one  of  them 
attained  to  a  real  comprehension  of  the  con- 
tinuity of  causes  in  the  sense  of  modern  exact 
science.  I  hope  also  to  show  that  the  existing 
antagonisms  resolve  themselves  into  a  higher 
unity  by  means  of  which  the  solution  of  the 
problem  becomes  again  surprisingly  simple,  a 
result  quite  common  in  cases  where  each  such 
antagonistic  principle  is  unduly  inflated  that 
it  may  redound  to  the  glory  of  its  school. 

Causes  and  Their  Identity  and  Equivalence 
With  Effects. 

While  the  modern  investigator  in  the  exact 
sciences  holds  the  conception  of  cause  and 
effect  only  in  a  unitary  or  monistic  sense,  and 
while  in  epistemology  there  is  a  similar  under- 
standing of  these  terms,  among  the  people  at 
large  the  word  cause  connotes  quite  different 
meanings.  Sometimes  the  word  is  used  in  the 
same  sense  as  it  is  by  the  man  of  science  ; 
such  a  case  is  the  recognition  in  reference  to 
an  explosion  that  the  degree  of  destruction  is 
dependent  upon  the  kind  and  quantity  of  the 
explosive  material.  Sometimes,  however,  we 
characterize  as  the  cause  the  spark  or  the  elec- 
tric current  which  precedes  the  explosion  and 
evokes  it.  In  the  first  case  the  cause  is  some- 


THE   CAUSE   OF   INFECTIOUS   DISEASE.         231 

thing  internal  and  exactly  concurrent  with  the 
effect,  in  the  second  case  the  cause  is  some- 
thing external  which  neither  qualitatively  nor 
quantitatively  stands  in  any  sort  of  congruent 
relation  with  the  effect.  In  order  to  eliminate 
this  double  sense  of  the  word  cause  and  to 
put  an  end  to  all  confusion,  a  general  agree- 
ment as  to  its  usage  was  reached  in  connection 
with  the  discovery  of  the  law  of  the  conserva- 
tion of  energy  by  R.  Mayer  and  his  successors, 
and  this  usage  has  generally  been  conformed 
to  in  epistemology  also. 

If  potential  energy  or  the  capacity  for  doing 
work  is  transformed  into  kinetic  energy  or 
actual  work  the  two  are  equal  in  quantity. 
They  pass  over  quantitatively  into  one  an- 
other, and  the  work  appearing  as  effect  accu- 
rately corresponds  to  and  is  measured  by  the 
initial  capacity  for  work  as  cause.  The  true 
and  sufficient  cause  of  any  effect  is  always 
something  internal,  something  that  follows 
from  the  kind  and  amount  of  the  initial  en- 
ergy, and  from  that  quality  and  qiiantity  alone 
and  entirely.  This  is  the  conception  of  a 
cause, —  Ursache — ,  an  idea  which  the  German 
language  can  express  so  felicitously,  while 
other  languages  must  paraphrase  it  (in  Latin, 
e.  g.,  causa  prima  or  princeps,  to  which  the 
further  definition  causa  interna  and  vera  or 


232  BACTERIOLOGY. 

sufficient  are  necessary  for  completeness)  in 
order  to  represent  everything  that  the  prefix 
Ur  denotes  to  a  German.  It  is  the  absolute 
thing  "  that  exists  behind  all  change  and 
remains  primordially  the  same"  as  Helmholtz 
expressed  it.  This  alone  we  now  call  cause, 
—  Ursache, — both  in  the  exact  sciences  and  in 
epistemology,  and  we  accept  nothing  but  that 
conception  as  true  and  sufficient.  Only  what 
is  provided  for  in  the  cause  both  in  quality 
and  quantity  can  appear  as  effect,  and  every- 
thing that  appears  as  effect  already  exists  in 
quality  and  quantity  in  the  cause,  that  is,  in 
the  internal  organization. 

Resistances  and  External  Conditions. 

In  a  strict  sense  causes  may  pass  over  of 
themselves,  freely  and  spontaneously,  into 
their  effect,  as  when  a  thrown  or  lifted  weight 
immediately  falls.  In  practice,  as  a  rule,  this 
does  not  happen,  since  in  order  to  render  a 
definite  work  possible,  we  prevent  the  raised 
weight  from  immediately  falling  again  by 
hanging  it  up  by  a  cord  or  by  placing  a  sup- 
port under  it.  Such  a  resistance  to  the  im- 
mediate conversion  of  potential  energy  into 
work  may  be  removed  in  a  given  case  easily 
or  with  difficulty,  and  a  corresponding  appli- 


THE   CAUSE   OF   INFECTIOUS   DISEASE.         233 

cation  of  external  energy  is  necessary  in  order 
to  do  away  with  the  resistance  and  so  bring 
about  the  actual  fall  of  the  weight  just  at  the 
right  moment.  The  removal  of  the  resistance, 
as  compared  with  the  actual  conversion  of  the 
capacity  for  work  into  work,  is  in  itself  some- 
thing purely  adventitious  ;  the  conversion 
comes  about  now  easily,  now  with  difficulty, 
now  in  this  way,  now  in  that,  according  to  the 
given  external  conditions.  When  uncertainty 
existed  about  such  connection,  therefore,  the 
expression  "  occasional  causes "  used  to  be 
employed.  Such  modifying  conditions  are  not 
necessary  to  the  effect,  they  have  not  in  them- 
selves the  character  of  true  causes,  but  they 
are  practically  important.  Corresponding  to 
every  form  of  potential  energy  there  exist  by 
virtue  of  the  external  conditions,  definite  initial 
circumstances  and  kinds  of  resistance  which 
determine  whether  a  given  form  of  potential 
energy,  a  given  possibility  of  work,  a  given 
internal  cause  can  be  converted  easily  or  with 
difficulty  or  not  at  all  into  kinetic  energy,  into 
work,  into  effect.  So  long  therefore  as  the 
external  conditions  remain  the  same,  the  same 
form  of  potential  energy  must  be  convertible 
with  the  same  ease  into  kinetic  energy,  the 
cause  into  the  effect.  If  the  conditions  change, 
then  the  transformation  may  take  place  more 


234  BACTERIOLOGY. 

easily  or  with  more  difficulty  or  not  at  all, 
since  by  altering  the  conditions  the  nature  and 
amount  of  the  resistance  may  be  changed. 
This  quantitative  conception  of  conditions  was 
first  set  forth  by  me  at  the  Naturalists'  Meet- 
ing in  Nuremberg  in  1893,  and  Mach  at  the 
same  time  showed  that  the  constancy  of  con- 
ditions is  full  of  significance  likewise  for  the 
constancy  of  physical  processes. 

The  Liberation  of  Energy. 

If  the  conversion  of  cause  into  effect,  of  poten- 
tial energy  into  kinetic  energy  is  prevented  by 
any  sort  of  resistance,  such  conversion  can 
obviously  take  place  only  if  this  resistance  is 
removed.  This  process  may  be  •  called,  with 
R.  Mayer,  the  liberation  of  energy,  and  the 
external  forces  which  accomplish  this  are 
called  liberating  impulseSo  I  have  shown  that 
we  cannot  content  ourselves  with  neglecting 
these  liberating  impulses  as  of  minimal  amount, 
but  that  they  are  connected  in  a  definite  and 
quantitative  way  with  the  liberation  of  energy ; 
the  impulse  must  always  introduce  energy 
enough  to  overcome  the  resistance. 

All  changes  of  one  form  of  energy  into  an- 
other are  visible  or  invisible  movements,  and 
the  impulses  that  set  free  the  energy  are  like- 


THE   CAUSE    OF   INFECTIOUS   DISEASE.         235 

wise  transmissions  of  a  movement.  Because 
of  the  continuity  of  energy,  therefore,  every 
form  of  liberated  energy  acts  through  the 
transmission  of  movement  in  such  a  way  as  to 
set  free  other  forms  of  energy.  In  the  pro- 
cesses of  disease  external  signs  of  this  process 
are  afforded  in  the  succession  of  changing 
symptoms.  The  impulses  that  set  free  energy 
are  something  external,  and  under  certain 
conditions  may  be  altogether  lacking  ;  it  is  at 
least  redundant  to  speak  of  liberating  causes. 

We  now  know  of  course  that  small  causes 
produce  not  great,  but  only  small  effects, 
whereas  small  impulses,  when  of  sufficient 
power  to  overcome  resistances,  may  set  free 
great  effects.  The  effect  is  always  a  process, 
not  an  entity,  and  the  causes  which  alone  pro- 
duce the  effect  are  internal.  External  con- 
ditions and  external  impulses  are  always  links 
of  unequal  value  in  an  endless  chain  in  which 
a  movement  exists.  Breaking  the  chain  at  any 
one  point  makes  the  production  of  the  effect 
impossible. 

It  is  in  itself  a  matter  of  complete  indiffer- 
ence what  notation  one  adopts.  I  have  myself 
decided  upon  a  definite  and  unambiguous  ter- 
minology and  thus  reached  clear-cut  and  defi- 
nite conceptions.  Such  a  terminology  is  ap- 
plicable in  all  realms  of  human  science,  and 


236  BACTERIOLOGY. 

therefore  should  make  an  end  once  for  all  of 
the  loose  terminology  which  has  been  in  vogue 
in  medicine.  When  I  presented  this  view  at 
the  Naturalists'  Meeting  in  1893,  the  objection 
was  made  from  various  sources  that,  in  view 
of  the  incomplete  theoretical  knowledge  and 
scientific  training  possessed  by  many  phy- 
sicians, my  exposition  was  somewhat  too  recon- 
dite. I  have  tried  now  in  this  way  to  make  it 
sufficiently  clear  that  in  the  exact  sciences 
there  is  absolutely  no  place  for  the  toys  of 
ontology,  for  entities  or  for  essences,  but  that 
we  must  deal  with  dynamic  phenomena,  with 
processes  which  interlock  with  one  another. 
That,  I  trust,  is  the  plain  sense  of  my  detailed 
exposition. 

I  now  hope  also  to  show  in  a .  way  intelli- 
gible to  my  readers  that  even  in  the  organic 
kingdom  and  especially  as  regards  the  doc- 
trine of  the  origination  of  infectious  disease 
we  have  no  place  for  the  "  entities  "  of  Syden- 
hq,m's  "  specific  disease,"  or  of  Virchow's  dis- 
eased cells,  or  of  Pettenkofer's  determining  cir- 
cumstances of  time  and  place,  or  of  Pasteur's, 
Kleb's,  F.  Cohn's,  and  Koch's  "  specific  " 
disease- producing  bacteria.  I  hope  further  to 
show  that,  in  considering  the  origination  of 
infectious  disease  and  the  dynamic  processes 
which  are  concerned,  we  can  take  account  of 


THE   CAUSE   OF   INFECTIOUS    DISEASE.         237 

all  these  things  without  degenerating  into  the 
mysticism  of  ontology.  Although  Behring 
rates  it  as  one  of  Koch's  services  to  science 
that  he  established  the  entity  of  disease  by 
setting  forth  the  bacteria  as  the  specific  cause, 
yet  it  is  clear  that  in  adopting  such  a  con- 
ception scientific  medicine  would  take  a  long 
step  backwards.  In  such  a  confusing  state  of 
affairs  a  clear  and  unambiguous  terminology 
has  always  been  an  advantage.  This,  how- 
ever, some  of  my  opponents  who  are  adherents 
of  the  bacteriological  ontology,  did  not  seem 
to  appreciate,  because  it  is  advantageous  for 
any  exploded  theory  to  have  a  vague,  ambigu- 
ous nomenclature.  This  is  plainly  in  order 
that  its  advocates  may  be  able  to  say,  after 
each  'new  victory  of  science,  that  they  had 
always  really  meant  something  quite  different 
from  what  every  reader  of  their  works  had 
previously  supposed  them  to  mean. 

Atomic  Combinations  and  Resistances. 

When  organic  substances  are  built  up  out 
of  the  elements  or  out  of  very  simple  com- 
pounds, there  always  restilts  as  the  product  of 
such  a  synthesis  not  only  an  increased  number 
of  atoms  in  the  molecule  but  an  increased 
number  of  combinations  of  atoms.  The  indi- 


238  BACTERIOLOGY. 

vidual  atoms  are  more  firmly  bound  to  one 
another  in  the  very  simple  molecules  that 
serve  as  a  starting-point  than  they  are  in  the 
complicated  synthetic  products.  Carbonic  acid 
and  water,  out  of  which  starch  and  sugar  are 
formed  by  green  plants,  are  simple  molecules, 
and  the  atoms  in  the  molecule  are  firmly 
united  as  compared  with  the  more  complicated 
and  more  unstable  molecules  of  starch  and 
sugar  formed  out  of  the  same  atoms.  Car- 
bonic acid,  water,  sulphuretted  hydrogen,  am- 
monia, and  nitric  acid,  all  of  which  may  enter 
into  the  synthesis  of  proteid  are  very  simple, 
stable  atomic  compounds  compared  with  the 
loose  and  complicated  combinations  in  which 
these  same  atoms  are  bound  in  the  proteid 
molecules.  Along  with  an  increase  in  the 
number  of  atoms  in  the  molecule  not  only  the 
number  of  atom-groupings  increases,  but  gen- 
erally also  the  looseness  of  combination.  Con- 
versely also,  if  a  complicated  and  unstable 
molecule  be  broken  down,  and  fall  to  pieces 
into  simpler  and  more  stable  compounds,  the 
ease  with  which  the  breaking-down  is  accom- 
plished and  the  number  of  possible  new  com- 
binations must  be  in  general  dependent  upon 
the  complexity  of  the  demolished  molecule. 
In  a  molecule  built  up  out  of  simple  com- 
pounds there  exists  just  as  much  energy  or 


THE   CAUSE   OF   INFECTIOUS   DISEASE.         239 

internal  cause  as  has  been  expended  in  its 
construction.  The  manner  in  which  the  atoms 
are  grouped  or  bound  together  produces  also 
a  definite  resistance  which  may  be  overcome 
with  more  or  less  difficulty. 

In  these  cases,  therefore,  the  resistance  bears 
a  much  closer  relation  to  the  store  of  potential 
energy  than  in  most  cases  in  inorganic  nature ; 
the  resistance  is  a  direct  consequence  of  the  pro- 
cess of  construction,  and  therefore  a  property 
of  the  molecular  structure.  In  the  structure 
and  constitution  of  every  organic  body  the  total 
amount  of  energy  which  may  manifest  itself 
as  effect  exists  as  the  potential  energy  of  com- 
bination, as  the  internal  cause.  The  kind  of 
energy  is  prefigured  also  in  the  molecular 
structure,  and  so,  finally,  is  the  kind  and 
amount  of  resistance  which  prevents  the  im- 
mediate and  free  transformation  of  cause  into 
effect.  I  have  explained  the  reasons  for  the  lat- 
ter phenomenon  briefly,  as  it  is  unnecessary  to 
consider  details  in  this  place.  The  looser  and 
more  manifold  the  atom-grouping  of  a  mole- 
cule is,  the  more  energy  the  molecule  con- 
tains ;  so  much  the  less  also  is  the  energy 
needed  to  overcome  the  resistance  and  liberate 
the  energy  of  the  molecule,  and  so  many  more 
are  the  different  kinds  of  external  impulses 
which  are  able,  by  the  application  of  aniso- 


240  BACTERIOLOGY. 

chronous  movements,  to  overcome  the  resist- 
ance and  convert  the  potential  energy  into 
kinetic,  the  cause  into  effect. 

In  purely  inorganic  processes  the  liberating 
impulses  either  bring  about  an  effect  or  do  not 
bring  it  about  according  to  the  extent  to  which 
they  are  quantitatively  adapted  for  the  re- 
moval of  resistance.  The  quantitative  effect 
of  the  liberating  impulses  bears  a  relation  to 
the  quality  of  the  potential  energy  set  free 
only  through  the  particular  form  of  motion 
involved.  In  the  liberation  of  the  energy  of 
complex  organic  molecules,  on  the  other  hand, 
the  impulses  bear  more  of  a  qualitative  rela- 
tion. But  whether  they  can  or  cannot  make 
themselves  felt  in  such  a  qualitative  way  again 
depends  in  the  last  instance  exclusively  upon 
the  character  of  the  molecular  structure.  The 
nature  and  amount  of  the  resistance  offered 
depend  also  upon  the  structure,  that  is  to  say, 
upon  the  internal  organization  of  the  organic 
substance  upon  which  a  liberating  impulse 
impinges.  Resistance  in  this  case  is  therefore 
in  plain  terms  a  result  of  adaptation,  while  in 
the  inorganic  realm  it  often  results  from  the 
simple  juxtaposition  of  different  processes  and 
their  reciprocal  action. 

Accordingly  in  our  inquiry  'into  the  causes 
of  organic  processes  we  meet  all  those  phe- 


THE    CAUSE    OF   INFECTIOUS   DISEASE.         24! 

nomena  that  we  find  in  inorganic  processes,  but 
they  are  better  regulated  and  more  intricate,  in 
the  first  place  because  of  adaptation,  and  in  the 
second,  because  of  the  complexity  of  the  phe- 
nomena involved.  We  find  various  forms  of 
potential  energy  or  internal  causes  which  may 
be  transformed  into  kinetic  energy,  into  work 
or  into  effect.  The  effect,  so  far  as  its  special 
features  are  concerned,  depends  solely  upon  the 
qualitative  character  of  the  compound,  that  is  to 
say,  the  mode  of  union  of  the  atoms  in  the 
molecule.  This  qualitative  relation  is  more 
striking  in  the  realm  of  the  organic  than  in 
the  inorganic,  where  it  has  been  recognized 
from  the  time  of  R.  Mayer  to  that  of  Hertz 
that  qualitative  relations  may  be  overridden. 
At  bottom,  however,  exactly  the  same  sub- 
jective limits  wall  us  in,  although  that  is  a 
fact  that  need  not  be  dwelt  upon  here.  Every 
quality  is  of  course  from  one  point  of  view  a 
sort  of  sense-illusion  or  sense-limit,  and  not 
anything  truly  objective.  We  find  forms  of 
resistance,  then,  which  result  from  character- 
istics of  molecular  structure  and  therefore  pre- 
sent not  only  the  well-known  quantitative  but 
also  a  qualitative  side  worthy  of  consideration. 
Finally  we  need  to  consider  the  liberating 
impulses  which  quantitatively  and  qualita- 
tively serve  to  remove  the  resistance.  We 
16 


242  BACTERIOLOGY. 

must  now  picture  the  problem  to  ourselves  in 
a  somewhat  different  way,  because  in  the  his- 
torical development  of  the  subject  the  aspect 
of  quality  so  predominated  that  the  quantita- 
tive side  was  wholly  overlooked  or  not  recog- 
nized, and  only  Liebig,  Lotze,  Virchow,  and 
Naegeli  suspected  the  existence  of  and  partly 
recognized  individual  factors  of  this  kind. 

The  explanation  of  the  fact  that  a  long  time 
elapsed  in  the  natural  sciences  before  the  dual- 
istic  contrast  between  organic  and  inorganic 
was  abandoned  is  that  the  conceptions  of 
the  Critique  lingered  long  in  men's  minds. 
Kant  was  a  dualist,  and  for  him  inorganic  pro- 
cesses were  the  consequences  of  necessity  ;  or- 
ganic processes,  of  purposiveness.  Schopen- 
hauer found  quantities  in  inorganic  processes, 
qualities  or  stimuli  in  organic.  Unfortunately 
dualism  in  the  latter  form  still  haunts  the 
minds  of  many  physicians  who  often  never  sus- 
pect its  retrogressive  character  as  compared 
with  the  mechanical  and  monistic  point  of  view. 

Predisposition  to  Disease  :    Acquired  and  In- 
herited. 

As  the  result  of  inheritance,  individual  de- 
velopment, and  adaptation  to  existing  condi- 
tions of  life,  every  man, — and  man  is  the  sub- 
ject I  place  from  now  on  in  the  foreground, — 


THE    CAUSE   OF   INFECTIOUS   DISEASE.         243 

possesses  within  his  organism,  that  is  in  his  or- 
gans, tissues,  cells  and  body-fluids,  at  a  given 
time  and  place,  a  definite  kind  and  amount  of 
potential  energy  or  cause.  This,  when  it  be- 
comes manifest,  we  designate  variously  as  a  phy- 
siological property  or  irritability,  as  a  morbid 
susceptibility,  as  a  predisposition  to  disease,  or 
as  immunity.  A  predisposition  to  certain  dis- 
eases exists  among  different  races  and  species. 
Negroes  for  example  are  infected  with  small- 
pox much  more  easily  than  Europeans,  while 
the  latter  not  only  sicken  more  easily  with  yel- 
low-fever but  the  disease  assumes  in  them  a 
more  fatal  character.  Variation  in  suscepti- 
bility to  disease  is  also  found  among  indivi- 
duals of  the  same  species,  as  is  established 
by  such  a  fact  as  that  among  our  popula- 
tion only  3  to  7  per  cent,  contract  cholera, 
while  others  of  the  population,  although  un- 
der the  same  conditions,  resist  the  disease. 
In  spite  of  the  ample  opportunities  of  infec- 
tion with  tuberculosis  which  are  afforded 
every  one,  only  some  20  to  25  per  cent,  of  the 
population  really  contract  any  form  of  the 
malady.  Indeed,  if  we  consider  the  most  dreaded 
of  all  known  infections,  the  Black  Death  of 
the  Middle  Ages,  we  are  told  that  only  one 
fourth  of  the  whole  population  of  Europe  con- 
tracted the  disease,  some  75  per  cent.,  therefore, 


244  BACTERIOLOGY. 

being  naturally  protected,  while  it  is  reported 
that  the  small-pox  in  Central  America  de- 
stroyed one-half  of  the  native  inhabitants. 

That  the  different  organs  of  the  body  pos- 
sess different  degrees  of  predisposition  to 
disease  may  be  inferred  from  the  fact  that 
diseases  which  are  now  known  to  be  infectious 
were  once  regarded  as  organic,  as,  for  instance, 
inflammation  of  the  lungs  and  catarrh  of  the 
intestine.  The  striking  fact  that  different 
organs  are  attacked  by  tuberculosis,  and  that 
the  disease  selects  different  organs  at  dif- 
ferent periods  of  life  beautifully  illustrates 
this  point.  The  experience  of  physicians,  and 
the  vast  material  placed  at  our  disposal  in 
statistics  of  disease  and  death  have,  in  short, 
shown  the  existence  of  a  predisposition  to  dis- 
ease and  have  made  it  clear  that  susceptibility 
to  different  diseases  varies  greatly  according 
to  the  period  of  life  and  according  to  sex. 

Plant  parasites  furnish  some  fine  examples 
of  predisposition.  Laboulbenia  muscce  is  found 
only  in  the  house-fly.  Cordyceps,  on  the  other 
hand,  occurs  in  the  larvae  of  different  butter- 
flies and  other  insects.  Phytophtora  infestans 
occurs  only  upon  potatoes,  while  Phytophtora 
omnivora  attacks  a  number  of  other  plants  but 
not  potatoes.  Species  of  moulds  of  the  genera 
Pythium  and  Sclerotinia  attack  only  plants 


THE   CAUSE   OF  INFECTIOUS   DISEASE.         245 

that  are  young  and  rich  in  water  and  therefore 
less  resistant,  but  do  not  attack  the  older  plants 
which  are  less  rich  in  water.  Cystopus  candi- 
dus,  according  to  De  Bary,  causes  the  white 
rust  of  the  garden-cress  (Lepidium  sativum)  ; 
all  plants,  in  fact,  are  susceptible  to  the  attack  of 
this  fungus,  but  only  when  they  are  in  the 
cotyledon  stage ;  when  the  cotyledon  falls  off 
the  leaf  becomes  resistant  and  the  spores  and 
germ-tubes  of  Cystopus  penetrate  only  locally 
in  every  case,  without  being  able  to  push  far 
into  the  interior.  The  blister-rust  of  spruce 
needles  occurs  according  to  Cramer  in  its  other 
parasitic  forms  only  upon  the  leaves  of  the 
Alpine-rose  and  wild  rosemary,  Chrysomyxa 
rhododendn 'and  ledi.  In  localities  where  these 
two  plants  do  not  occur  no  blister-rust  is  found 
upon  the  spruce.  Similar  relations  exist  ac- 
cording to  De  Bary,  between  the  rust  of  wheat 
and  the  aecidia  of  the  barberry.  The  "  local  " 
disposition  is,  therefore,  in  reality  the  local 
presence  of  the  host.  According  to  De  Bary, 
if  the  "  disease  predisposition  "  due  to  the  pre- 
sence of  the  host  be  removed — e.  g.,  if  the 
barberry  bush  be  banished  to  a  distance — the 
disease  disappears,  only  to  arise  again  when 
susceptible  host-plants  are  introduced. 

Perhaps  the  most  remarkable  fact  in   this 
connection  is  that  definite  predispositions  may 


246  BACTERIOLOGY. 

be  acquired  as  the  result  of  external  changes. 
An  attack  of  illness  due  to  "  catching  cold  "  or 
of  rheumatism — affections  causally  related  per- 
haps— increases  the  tendency  to  those  diseases, 
while  an  attack  of  any  one  of  the  more  acute 
infectious  diseases,  such  as  small-pox,  scarlet 
fever,  or  measles,  confers  immunity  against  an- 
other attack.  Susceptibility  to  disease  is  trans- 
muted into  protection  against  it.  Such  an  in- 
dividually acquired  immunity  can  be  handed 
on  from  mother  to  child.  I  shall  not  in  this 
place  broach  the  much  mooted  question  whether 
or  not  acquired  characters  can  be  inherited, 
and  shall  not  try  to  set  forth  here  how,  upon 
the  basis  of  my  representation  of  the  problem 
of  causation,  the  question  really  comes  within 
our  reach.  It  may  suffice  at  present  to  make 
clear  that,  under  certain  circumstances,  acquired 
characters,  among  which  may  be  reckoned  ac- 
quired tendency  to  disease  or  acquired  immunity, 
must  be  inherited.  According  to  Kaltenbach, 
twin-sisters,  originating  from  two  different 
ova,  were  exposed  in  equal  measure  to  in- 
fection from  scarlet  fever  ;  one  of  them  remained 
entirely  immune,  the  other  succumbed  imme- 
diately. The  latter  resembled  the  father,  the 
immune  child  the  mother,  who,  fourteen  months 
previously  had  experienced  a  severe  attack  of 
scarlet  fever.  Here  was  a  pronounced  inborn 


THE   CAUSE   OF   INFECTIOUS   DISEASE.         247 

quality,  but  this  quality  was  inherited,  and  the 
character  thus  transmitted  was  originally  ac- 
quired through  disease.  An  interesting  ob- 
servation has  been  made  in  certain  cases  of 
twins  and  triplets.  When,  by  infection  of  the 
mother  with  small-pox  opportunity  was  given 
for  placental,  intra-uterine  infection  of  all  the 
offspring,  one  or  another  of  the  children  re- 
mained free  from  the  disease,  although  the  pos- 
sibility of  infection  taking  place  by  means  of  the 
placenta  was  proved  by  its  occurrence  in  the 
case  of  one  or  more  of  the  children.  But  it  has 
also  been  observed  that  a  pregnant  woman  who 
had  been  successfully  vaccinated  gave  birth  to 
a  heal  thy  child  who  nevertheless  sickened  three 
years  later  with  small-pox,  and  in  another 
case  small-pox  was  observed  in  a  foetus 
whose  mother  had  previously  suffered  with  the 
disease.  Whether  an  acquired  disposition  is 
transmissible  depends  upon  the  kind  and  dur- 
ation of  the  influence.  On  this  point  it  is  easy 
to  deceive  oneself.  In  Ehrlich's  experiments 
in  regard  to  rendering  animals  resistant  to 
poisons,  at  first  sight  it  seemed  as  if  the  young 
inherited  immunity ;  another  interpretation 
proved,  however,  to  be  the  correct  one.  The 
young  of  a  non-immune  mother,  when  fed  on 
the  milk  of  an  immunized  mother,  acquired 
immunity,  thereby  showing  that  the  immunity 


248  BACTERIOLOGY. 

was  not  conveyed  by  direct  inheritance.  It  was 
instead  an  instance  of  extra-uterine,  individual 
immunization  brought  about  by  means  of  the 
protective  substances  contained  in  the  milk  of 
an  immune  mother  or  nurse.  According  to 
Tizzoni,  however,  immunity  to  tetanus  acquired 
by  the  father  can  be  transmitted  to  the  off- 
spring.1 

The  existence  of  a  definite  predisposition  to 
or  immunity  to  disease  is  dependent  upon  the 
inherited  organization  of  the  body,  and,  upon 
its  adaptation  to  the  conditions  of  life,  among 
which  may  be  numbered  not  only  soil,  water, 
air,  and  the  general  factors  of  weather  and  cli- 
mate, but  also  social  conditions.  These  chang- 
ing circumstances  or  external  conditions  act 
upon  the  internal  disposition  which  remains 
always  the  same.  If  these  conditions  change, 
then  readjustment  must  occur,  that  is,  changes 
in  the  internal  constitution  must  take  place. 
Every  change  in  environment,  every  consider- 
able change  in  nutrition  may,  therefore,  make 
itself  felt  by  its  effect  upon  our  predisposition. 
By  utilizing  the  information  gained  from  ex- 
periments along  this  line  we  have  at  our  dis- 
posal a  means  of  influencing  the  disposition  in 
our  favor,  as,  for  instance,  by  the  removal  of 

1  Later  experiments  have  failed  to  confirm  the  statement  that  an 
immune  father  can  transmit  immunity. — E.  O.  J. 


THE    CAUSE    OF  INFECTIOUS   DISEASE.         249 

social  mal-adjustments,  by  improvement  of  the 
locality  in  which  we  dwell,  by  changes  in  meta- 
bolism through  the  introduction  of  better  nu- 
triment, or  by  regulation  of  the  temperature 
conditions  of  the  body.  Finally,  we  are  able  to 
make  use  of  the  fact  that  by  undergoing  a 
disease  the  predisposition  to  that  disease  is 
removed  and  converted  into  its  opposite,  im- 
munity. 

In  no  case  can  anything  appear  in  the  form 
of  disease  which  was  not  previously  present  in 
the  body  as  a  predisposition ;  external  forces 
are  able  merely  to  make  this  predisposition 
apparent.  It  is  therefore  at  the  outset  im- 
portant to  hold  fast  to  the  fact  that  we  are  in 
a  position  to  act  upon  a  given  physiological 
organization  by  a  whole  series  of  changes  in 
external  conditions  ;  we  can  either  heighten  a 
predisposition  or  remove  it.  Herein  lies  also 
the  reconciliation  of  the  physician's  art,  which 
has  reference  to  the  individual,  with  the  official 
health  regulations,  which  have  regard  to  the 
conditions  making  for  the  betterment  of  all. 
When  the  physician,  by  thorough  observation 
and  investigation,  knows  the  conditions  that 
influence  a  given  disposition  in  a  definite  way, 
when  he  is  scientifically  trained  and  has  a  true 
conception  of  hygiene,  and  is  at  once  physician 
and  naturalist,  then  he  is  able  to  cure  disease 


250  BACTERIOLOGY. 

by  use  of  the  very  same  forces  which  serve  to 
create  or  alter  the  human  constitution.  In 
this  simple  sense  there  is  a  true  art  of  healing. 
The  external  conditions  to  which  a  human 
being  is  subjected  according  to  season  and 
locality  make  themselves  felt  throughout  the 
organs,  tissues,  and  cells  of  the  whole  body. 
This  they  do  through  the  mediation  of  meta- 
bolism and  by  the  aid  of  the  nervous  system, 
factors  that  determine  the  character  of  the 
synthesis  or  the  building  up  of  the  organism, 
and,  as  before  mentioned,  that  determine  also 
the  kind  and  amount  of  the  resistance  that 
hinders  release  of  energy.  We  are  accord- 
ingly set  the  further  task  of  guiding  the  course 
of  events  by  the  use  of  those  conditions  that 
create  resistances,  and  guiding  them  further- 
more in  such  a  way  that  the  physiological  resis- 
tances are  naturally  and  readily  overcome,  and 
the  liberation  of  energy  follows  easily  and  in 
normal  paths,  while  all  sorts  of  pathological 
resistances  are  avoided  and  the  pathological 
setting-free  of  energy  prevented.  Since  the 
kind  and  amount  of  resistance  met  with  in  the 
organic  kingdom  is  a  consequence  of  organic 
structure,  this  task  practically  coincides  with 
the  first,  namely  that  of  influencing  by  the  aid 
of  suitable  external  conditions  the  potential 


THE   CAUSE    OF   INFECTIOUS   DISEASE.         25! 

energy  or  the  cause,  or,  in  a  word,  the  disposi- 
tion of  men. 

Disease-Stimuli. 

The  liberating  impulses,  as  they  are  called 
in  the  inorganic  sciences,  are  called  stimuli  in 
speaking  of  normal  life-processes,  and  we  may 
speak  of  the  particular  stimuli  that  evoke  dis- 
ease as  excitants  of  disease,  as  Liebig  spoke 
of  the  excitants  of  fermentation. 

Through  a  depression  of  the  physiological 
organization  and  a  consequent  lowering  of  re- 
sistance, normal  physiological  stimuli  may 
become  disease  stimuli ;  or,  the  organization 
and  resistance  remaining  the  same,  a  normal 
stimulus  may  become  more  intense  and  be 
converted  into  a  disease  stimulus  ;  in  other 
words,  the  stimulus  may  come  into  play  only 
quantitatively.  If  this  be  so,  it  is  easy  to 
understand  how  the  kind  of  effect  that  we  call 
disease  depends  qualitatively  upon  the  kind  of 
organ,  tissue,  or  cell  concerned,  and  indeed 
solely  upon  these  and  their  internal  adjust- 
ments (Virchow).  If  the  disease  stimulus, 
however,  be  a  living  thing,  then,  according  to 
Koch's  conception,  this  natural  law  would  be 
summarily  abolished  and  the  quality  of  the 
disease  stimulus,  that  is  to  say,  the  kind  of 
disease-producing  bacteria,  would  determine 


2$2  BACTERIOLOGY. 

the  disease,  or  bring  about  the  effect.  We 
find  only  apparent  support  for  this  latter  view 
from  such  facts  as  that  anthrax  bacteria  always 
evoke  anthrax,  and  tubercle  bacilli  tuberculosis 
in  susceptible  animals,  and  that  many  diseases, 
such  as  malaria  and  pneumonia,  have  a  typical 
and  often  cyclical  course.  If  the  facts  are 
considered  attentively,  they  reveal  a  state  of 
affairs  really  quite  different.  If  we  suppose 
that  the  pathogenic  'bacteria  are  "  specific  en- 
tities," that  they  are  the  true  and  sufficient 
cause  of  disease  as  Pasteur  and  Koch  have 
affirmed,  then  at  least  four  conditions  would 
have  to  be  fulfilled.  First,  the  disease-pro- 
ducing bacteria  should  exert  no  other  effect 
than  that  of  producing  disease  ;  second,  their 
ability  to  produce  disease  should  remain  con- 
stant ;  third,  they  should  affect  all  animals  in 
the  same  way  without  reference  to  particular 
species  ;  and  fourth,  they  should  produce  only 
a  single,  sharply  defined,  typical  and  "  specific  " 
infectious  disease.  In  such  a  way  as  this  Koch 
has  really  pictured  things  to  himself, — this  is 
indeed  the  leading  motive  of  his  school — while 
Pasteur  who  also  originally  looked  upon  the 
question  in  the  same  way,  later  adopted  other 
opinions.  The  dogma  of  the  "  specificity  "  of 
the  minute  organisms  that  excite  disease,  the 
belief  in  the  existence  of  pathogenetic  or  pa- 


THE   CAUSE   OF  INFECTIOUS   DISEASE.        253 

thogenic  bacteria,  meaning  thereby  belief  in 
unvarying  specific  character  and  physiological 
effect,  was  especially  developed  by  Henle  and 
later  was  worked  out  by  Davaine,  Pasteur,  J. 
vSchroter,  F.  Cohn,  Klebs,  and  Koch.  Other 
investigators,  among  whom  I  need  name  only 
Naegeli  and  Billroth  as  the  leaders,  have  main- 
tained, in  opposition  to  this  view,  that  bacteria 
are  constant  neither  in  kind  nor  in  action. 

Now  in  the  first  place,  are  disease-producing 
bacteria  capable  of  producing  any  other  effect 
than  that  of  disease  ?  By  the  modern  method 
of  pure  cultures  it  has  been  established  beyond 
all  doubt  that  disease-producing  bacteria  do 
indeed  display  other  activities  ;  the  successful 
culture  of  pathogenic  bacteria  is  in  itself  a 
proof  that  such  bacteria  are  not  restricted  to 
a  parasitic  existence  and  to  the  exciting  of 
disease.  Thus  for  example  the  bacteria  of 
glanders  develop  a  brown  pigment  upon 
potato  •  the  cholera  bacteria  form  a  yellow 
or  brown  pigment  upon  potato  and  in 
sugar  solutions  cause  an  acid  fermenta- 
tion ;  the  so-called  golden  pus  cocci,  which 
are  the  most  common  pyogenic  bacteria, 
form  in  cultures  a  splendid  yellow  pigment 
and  in  sugar  solutions  produce  acid.  Whereas 
formerly,  in  accordance  with  F.  Cohn's  view, 
bacteria  were  distinguished  according  to  their 


254  BACTERIOLOGY. 

"  specific  "  activities  and  characters  into  dis- 
ease-producing or  pathogenic,  fermentation- 
causing  or  zymogenic,  and  pigment-forming 
or  chromogenic,  the  foregoing  examples  show 
that  a  single  bacterial  species,  a  single  "  spe- 
cific "  minute  living  thing  is  capable  of  exercis- 
ing all  three  of  the  specific  activities  formerly 
held  to  be  essentially  distinct.  The  "  specific  " 
bacteria  are  therefore  not  the  true  cause  ;  that 
lies  in  the  character  of  the  nutrient  medium  ; 
the  bacteria  can  elicit  only  what  is  preformed  in 
the  structure  of  the  medium.  I  have  given  the 
name  of  "  cycle  of  activity  "  to  this  class  of  phe- 
nomena. These  facts  plainly  militate  against 
the  doctrine  of  "  specific  "  disease  germs  held 
by  Cohn  and  Koch,  and  they  help  us  to  un- 
derstand one  important  thing  concerning  the 
production  of  disease,  namely  that  it  is  not  the 
transferable  u  essence  "  that  determines  the 
character  of  the  "  specificity  "  of  disease,  but 
the  similarity  and  the  permanency  of  the 
conditions  of  life.  Since  disease  germs  that 
are  presumed  to  be  "  specific "  are  able  to 
cause  fermentations  and  to  form  pigments,  it 
is  clear  that  a  close  relation  exists  between  the 
"  parasitic  "  bacteria  occurring  in  living  human 
beings  and  the  so-called  "  saprophytic  "  bac- 
teria, or  bacteria  of  putrefaction,  which  are 
able  to  live  outside  of  the  human  body  upon 


THE  CAUSE   OF   INFECTIOUS   DISEASE.        255 

dead,  lifeless,  organic  or  inorganic  material. 
Such  relations  are  sometimes  very  easily  traced, 
but  are  often  obscure  and  in  other  cases  are 
wanting.  The  parasitic  organisms  may  ac- 
cordingly be  separated  into  obligatory  para- 
sites, facultative  saprophytes,  and  facultative 
parasites. 

In  the  group  of  obligatory  parasites  the  de- 
pendence upon  processes  of  putrefaction,  and 
the  ability  to  live  at  the  cost  and  by  the  destruc- 
tion of  lifeless  food  material,  have  gradually 
been  completely  lost,  or  at  least  such  relations 
have  up  to  the  present  not  been  made  out.  In 
this  group  may  belong  perhaps  the  yet  undis- 
covered germs  of  the  so-called  acute  exanthe- 
mata like  smallpox,  scarlet-fever  and  measles, 
and  also  the  germ  already  discovered  in  re- 
lapsing fever.  The  facultative  saprophytes 
are  those  germs  that  we  find  as  a  rule  living 
as  parasites,  but  which,  under  special  conditions, 
can  maintain  themselves  also  upon  lifeless 
material,  and  by  breaking  down  this  lifeless 
nutrient  substance  are  able  to  grow,  multiply 
and  perpetuate  the  species.  Such  a  sapro- 
phytic  condition  has  been  brought  about  in  the 
case  of  the  tubercle  bacillus  by  Koch  and 
by  Fischel,  one  of  my  pupils,  and  I  was  able 
to  show  that  this  organism,  which  up  to  that 
time  had  been  called  tubercle  bacillus  is  only 


256  BACTERIOLOGY. 

the  parasitic  form  of  a  pleomorphic  microbe,  trie 
other  forms  of  which  make  their  appearance 
only  in  the  course  of  its  saprophytic  existence 
and  were  hence  at  first  entirely  overlooked. 
The  group  of  facultative  parasites  comprises 
those  species  which  can  maintain  and  repro- 
duce themselves  in  a  purely  saprophytic  way 
upon  lifeless  material  without  ever  necessarily 
attacking  living  hosts  as  parasites  ;  indeed  to 
attain  certain  stages  of  development  it  is  neces- 
sary that  they  should  live  the  life  of  real 
saprophytes.*  To  this  latter  group  belong  the 
majority  of  the  disease-producing  bacteria  now 
known,  such  as  the  bacteria  of  anthrax,  typhoid 
fever,  and  cholera. 

Finally,  there  are  bacteria  which  in  a  strict 
sense  never  invade  the  living  organism,  but 
yet  are  dangerous  and  able  to  provoke  disease. 
Many  of  the  bacteria  of  putrefaction  are  able 
to  generate  out  of  lifeless  nutrient  substances 
poisons  that  can  act  injuriously  on  human  be- 
ings without  participation  of  the  poison-forming 
bacteria  themselves.  This  may  even  happen  in 
the  normal  organism  during  intestinal  putre- 
faction, a  process  which  seems  in  itself  to  have 
become  necessary  as  a  result  of  adaptation. 
Such  bacteria  may  be  designated  as  ceco-para- 
sites,  and  may  be  regarded  as  forms  on  the 
road  to  become  facultative  parasites. 


THE   CAUSE   OF   INFECTIOUS  DISEASE.        257 

The  organism  may  also  be  affected  through 
the  removal  of  protective  structures  of  the 
body  by  the  action  of  putrefactive  poisons  ;  for 
example,  the  intestinal  epithelium  may  be 
destroyed  ;  saprophytes  may  then  enter  into 
the  dead  tissues,  and  may  even  penetrate  still 
farther  into  the  body,  as  for  instance  into  the 
nearest  lymph  glands.  The  common  bac- 
terium of  the  large  intestine,  B.  coli  communis, 
can  do  this.  There  are  found,  furthermore, 
transition  forms  between  the  different  groups 
of  parasitic  microbes,  so  that  it  is  evident  that 
we  are  not  here  dealing  with  rigid  groups,  but 
only  with  a  division  which  enables  us  to  recog- 
nize more  easily  the  characters  important  from 
a  human  standpoint.  In  the  process  of  putre- 
faction, then,  a  process  which  forms  an  abso- 
lutely necessar}r  link  in  the  cyclical  course  of 
matter,  are  found  represented  the  fundamental 
phenomena  of  parasitism  out  of  which  by  de- 
velopment and  adaptation  to  living  hosts  the 
various  and  more  advanced  stages  of  parasitism 
have  arisen. 

Putrefaction  may  exert  in  other  respects  an 
important  influence  upon  the  excitation  of  dis- 
ease ;  volatile  or  soluble  poisons  of  putrefaction 
may  weaken  the  living  organism  so  that  it  can 
be  attacked  more  easily  and  successfully  by 

the  true  parasites  or  by  their  toxins.     The 
17 


258  BACTERIOLOGY. 

mere  presence  and  growth  of  certain  sapro- 
phytes acts  in  such  a  way  that  disease  germs 
following  in  their  wake  can  get  lodgment  upon 
man  the  more  readily,  while  on  the  other  hand 
other  saprophytes  may  hinder  the  lodgment  of 
pathogenic  organisms.  Among  the  various 
effects  produced  by  saprophytic  microbes  out- 
side and  inside  a  living  host  must  be  included 
those  that  either  favor  or  hinder  the  lodgment 
and  action  of  disease  germs.  That  is  to  say, 
these  microbes  act  upon  the  disposition  toward 
disease.  They  present  therefore  only  individ- 
ual cases,  albeit  particularly  difficult  to  evalu- 
ate, of  external  relations  or  conditions  which 
may  now  exalt  an  existing  disposition  to  dis- 
ease, now  diminish  it  or  remove  it  altogether. 
This  explanation  should  make  it  no  longer 
difficult  for  the  reader  to  understand  the  very 
various  modes  of  action  of  disease-germs  in 
man,  since  every  possibility  of  action  has  de- 
veloped out  of  two  activities  already  manifested 
in  the  process  of  putrefaction,  namely  out  of 
the  formation  of  poisons  by  bacteria,  and  out  of 
bacterial  growth  and  multiplication.  At  one 
extreme,  therefore,  we  find  a  kind  of  parasitic 
action  in  which  not  the  bacteria  themselves 
but  the  poisons  formed  by  them  and  absorbed 
into  the  circulation  are  the  more  important 
factor,  while  upon  the  other  side  stand  those 


THE   CAUSE   OF   INFECTIOUS   DISEASE.         259 

parasites  which  act  especially  through  the  for- 
mation of  local  growths  or  tumors.  To  the 
latter  class  belong  the  germs  causing  tumors, 
which  have  been  investigated  with  especial 
accuracy  among  plants,  and  a  well-known  ex- 
ample of  which  is  the  germ  of  human  tuber- 
culosis ;  to  the  former  belong  the  germs  of 
diphtheria  and  tetanus  ;  the  cholera  germ  also 
approximates  to  the  former  group.  Between 
these  extremes  stand  the  other  pathogenic  bac- 
teria :  in  some  the  proliferation  of  the  bacteria, 
in  others  their  production  of  poison  is  the  pre- 
dominant factor.  Disease-producing  bacteria 
may  therefore  affect  man  in  very  different 
ways.  They  may  cause  changes  by  growing 
and  multiplying  in  vital  organs  and  through 
thus  altering  the  metabolism  of  important  tis- 
sues may  influence  unfavorably  the  metabol- 
ism of  the  whole  body  ;  or  they  may  rob  the 
body  of  important  nutrient  material  and  intro- 
duce the  products  of  their  own  metabolism 
into  the  body  of  their  host :  or  they  may,  in 
the  act  of  satisfying  their  own  need  of  energy, 
split  off  from  the  proteids  of  the  human  body 
certain  substances  which  act  upon  man  as  poi- 
sons ;  or  they  may  themselves  generate  poisons 
in  their  own  bodies  and,  like  poisonous  plants, 
be  in  themselves  poisonous.  The  mode  of 
action  may  vary  according  to  conditions  ;  for 


260  BACTERIOLOGY. 

example,  ergot  is  a  local  growth  for  the  grain, 
a  poison  for  man. 

In  all  cases,  from  the  simple  germs  of  putre- 
faction and  the  ceco-parasites  up  to  the  obliga- 
tory parasites,  one  thing  is  a  pre-requisite  to 
successful  invasion,  namely,  that  as  compared 
with  the  mechanical  or  chemical  attacking 
powers  of  the  microbe  the  mechanical  and 
chemical  resisting  powers  of  man  be  relatively 
feeble  or  impaired.  If  this  is  not  the  case  the 
human  organism  either  does  not  allow  the  germ 
to  gain  entrance  to  the  body,  or  when  entrance 
is  effected  it  nullifies  the  poisonous  action  by 
a  counteraction. 

After  what  has  now  been  stated  no  particular 
assurance  is  necessary  that  bacteria  and  other 
minute  pathogenic  organisms  do  not  exercise 
their  injurious  effect  upon  man  from  an  inbred 
wickedness  and  pleasure  in  doing  mischief,  but 
that  in  the  phenomena  of  parasitism  we  have 
to  do  simply  with  questions  of  adaptation,  with 
the  utilization  of  situations,  so  to  speak,  which 
man  himself  provides  by  his  own  sins  of  hy- 
gienic omission  and  commission,  and  which 
therefore  he  himself  is  able  to  remove.  The 
germs  of  putrefaction  dispose  of  the  dead  bodies 
of  all  organisms  in  nature,  simply  to  satisfy 
their  own  need  of  energy  and  the  conditions 
of  their  own  metabolism.  This  is  also  the  case 


THE   CAUSE   OF   INFECTIOUS   DISEASE.        261 

when  they  adapt  themselves  to  the  conditions 
of  intestinal  putrefaction.  They  may  for  the 
same  reason  invade  the  living  organism  when- 
ever its  normal  protecting  power  has  become 
enfeebled  through  errors  in  l^giene. 

The  second  question  is,  Do  the  so-called 
"  specific  "  disease  germs  vary  in  their  capacity 
to  produce  disease  ?  Buchner  was  the  first  to 
succeed,  upon  the  basis  of  systematic  experi- 
ments, in  proving  that  the  so-called  anthrax 
bacilli  can  be  modified  artificially  in  such  a  way 
that  they  are  no  longer  able  to  bring  about  any 
illness,  but  behave  like  perfectly  harmless 
saprophytes.  The  same  discovery  was  soon 
afterwards  made  accidentally  by  Pasteur  in  re- 
gard to  the  bacteria  of  the  disease  called  chicken 
cholera,  and  we  now  know  from  hundreds  of 
experiments  that  no  peculiarity  of  disease-pro- 
ducing bacteria  is  more  easily  affected  than  the 
very  capacity  in  question,  commonly  presumed 
to  be  "  specific,"  namely  that  of  producing  dis- 
ease. The  physician  who  seeks  the  "  essence  " 
of  the  disease  in  the  "  specificity  "  of  the  disease 
germs  can  plainly  attach  importance  only  to 
those  parasites  whose  "  specific  "  capacity  of 
producing  disease  is  invariably  exercised. 
The  facts  that  demonstrate  the  variability  of 
this  capacity  therefore  obviate  all  need  for  seek- 
ing an  "essence." 


262  BACTERIOLOGY. 

The  third  question  is  this :  Do  the  same 
"  specific "  disease  germs  affect  all  animals 
with  the  same  typical  disease  ?  This  question 
must  also  be  answered  in  the  negative.  We 
see  that  each  kind  of  disease  germ  affects  only 
certain  hosts  ;  syphilis,  leprosy,  cholera  and 
typhoid  fever  are  known  only  in  man,  while 
tuberculosis,  glanders  and  anthrax  attack 
both  man  and  certain  kinds  of  animals. 
Further  illustrations  are  given  on  p.  243  and 
in  the  chapter  treating  of  the  individual  species 
of  bacteria  ;  others  will  be  brought  forward 
later. 

The  fourth  question  is,  Does  a  "  specific  " 
disease  germ  cause  only  one  disease  ?  We 
may  distinguish  in  this  inquiry  two  groups 
of  phenomena.  In  the  first  group  belong  those 
facts  showing  that  similar  symptoms  may  be 
evoked  and  that  the  same  organs  or  tissues 
may  suffer  anatomically  similar  changes 
through  the  action  of  entirely  different  germs. 
For  example,  the  formation  of  nodules  or  tu- 
bercles in  connective  tissue  may  be  brought 
about  by  the  germs  of  syphilis,  leprosy,  gland- 
ers, and  tuberculosis ;  suppiiration  can  be 
caused  by  the  germs  of  wound  erysipelas,  the 
tubercle  bacilli,  the  anthrax  bacilli,  and  the 
germs  of  typhoid  fever  and  pneumonia  ;  both 
the  common  bacteria  of  the  colon  and  the  chol- 


THE   CAUSE   OF   INFECTIOUS    DISEASE.         263 

era  bacteria  can  incite  diarrhoea  ;  the  bacteria 
of  tuberculosis,  of  typhoid  fever  and  pneumonia 
may  produce  inflammation  of  the  pia  mater ; 
tubercle,  typhoid,  and  pneumonia  bacteria, 
gonococci,  staphylococci,  and  streptococci,  may 
cause  endocarditis ;  the  phenomena  of  blood- 
poisoning  are  caused  by  a  whole  series  of  bac- 
teria. In  these  cases,  therefore,  the  determin- 
ing cause  resides  in  the  tissues  and  their 
disposition,  not  in  entirely  distinct  kinds  of 
bacteria. 

The  second  group  of  facts,  belonging  with 
these  but  obtained  in  another  way,  demonstrate 
that  one  and  the  same  "  specific  "  disease  germ 
may  produce  very  different  affections.  Diph- 
theria bacilli,  for  example,  may  occasion  local 
diphtheria  or  paralysis  or  acute  blood-poison- 
ing ;  the  bacteria  of  erysipelas  may  bring  about 
erysipelas  in  the  skin,  but  are  able  also  to  pro- 
duce suppuration  or  inflammation  of  the  lungs ; 
the  pneumonia  germs  may  cause  typical  pneu- 
monia, blood-poisoning,  inflammation  of  the 
cerebral  membranes,  or  inflammation  and  sup- 
puration of  the  middle  ear ;  tubercle  bacilli 
excite  tubercle  formation  in  connective  tissue, 
inflammation  of  the  cerebral  membranes,  sup- 
puration and  true  consumption  or  phthisis. 
The  preceding  sections  contain  still  other  ex- 
amples. 


264  BACTERIOLOGY. 

Perhaps  still  a  third  group  might  be  added, 
comprising  the  critical  diseases  like  intermit- 
tent fever,  relapsing  fever  and  pneumonia. 
Many  observers  suppose,  in  accord  with  Henle, 
that  the  germs  of  these  diseases  in  man  have 
a  course  of  development  sharply  defined  by 
hours  or  days,  and  that  therefore  the  life-cycle 
of  the  germ  determines  the  cycle  of  the  disease. 
So  far,  however,  as  we  know  anything  about 
these  germs,  we  never  find  such  remarkable 
cycles  occurring  outside  of  the  human  body. 
The  pneumonia  germs  cause  crises  only  in  man, 
while  in  rabbits  they  bring  about  simple  blood- 
poisoning  without  any  cycle.  In  cultures  they 
show  no  regular  cyclical  character  at  all.  For 
these  reasons  I  am  inclined  to  seek  the  basis 
of  such  cyclical  manifestations  in  peculiarities 
of  the  human  organization,  and  the  more  so 
that  even  in  man  pneumonia  may  sometimes 
occur  without  crisis  and  show  a  resemblance 
to  forms  of  blood-poisoning.  I  have  already 
mentioned  the  conflicting  views  of  Golgi  and 
Laveran  respecting  malarial  fever. 

Upon  sifting  all  the  available  material,  I  can- 
not find  a  fact  which  is  in  real  harmony  with 
Koch's  conception  of  "  specific"  disease-germs. 
I  must  protest  also  against  the  view  held  by 
Billroth  and  Naegeli,  which  is  extreme  and 
one-sided,  and  I  expressly  acknowledge  that  we 


THE   CAUSE   OF  INFECTIOUS   DISEASE.        265 

can  distinguish,  species  and  genera  among  bac- 
teria and  other  minute  organisms.  Such  con- 
stancy as  we  observe,  however,  is  not  the  mysti- 
cal constancy  of  "  specific  "  essences,  but  a  con- 
stancy made  possible  by  the  permanence  of  the 
environment.  Micro-organisms  change  with 
the  changes  in  their  surroundings,  and  the 
placing  of  this  fact  on  a  sure  footing  consti- 
tutes the  great  advance  that  modern  bacteri- 
ology has  made  beyond  the  standpoint  reached 
by  Koch. 

Just  as  the  human  being  possessed  of  a  def- 
inite organization  is  compelled  continually  to 
adapt  himself  to  changing  conditions  of  life,  so 
is  the  microbe  also  constrained  to  the  same  task. 
In  the  majority  of  men  the  bodily  constitution 
is  always  oscillating,  manifesting  now  increase, 
now  decrease  of  a  definite  disposition  toward 
disease.  The  microbes  also  vary  according  to 
the  conditions  imposed  upon  them  and  display 
increased  or  decreased  capacity  to  grow  or  form 
poisons  in  the  human  body,  capacity  in  other 
words  to  remove  with  greater  or  less  difficulty 
the  resistance  inherent  in  the  human  organi- 
zation. Accordingly  we  observe  the  occurrence 
sometimes  of  mild,  sometimes  of  severe  epi- 
demics, and  in  every  epidemic,  along  with  the 
"  typical  "  cases,  we  find  especially  grave  or 


266  BACTERIOLOGY. 

especially  light  cases  which,  do  not  conform 
to  the  schema. 

If  we  diminish  the  disposition  of  a  man  to- 
ward a  disease  we  influence  his  organization  in 
the  sense  of  exalting  its  resistance  to  infection. 
In  this  way  the  same  effect  is  produced  as  when 
we  diminish  the  "  contagious  "  or  toxic  quality 
of  the  disease  germ,  the  disposition  of  the  man 
to  the  disease  remaining  the  same.  The  or- 
dinary anthrax  bacteria,  for  example,  cause 
in  guinea-pigs  a  generalized  blood-poisoning 
which  is  speedily  fatal,  and  in  dogs,  which  are 
naturally  immune  toward  this  disease  they 
cause  at  most  an  abscess,  or  a  local  suppuration. 
But  if  we  diminish  to  a  certain  extent  the  dis- 
ease-producing power  of  the  anthrax  bacilli, 
they  provoke  in  the  otherwise  very  susceptible 
guinea-pig  merely  a  local  suppuration,  which 
readily  heals. 

The  disease  germs  remaining  constant,  it  is 
possible  to  heighten  natural  predisposition  to 
disease  by  starving  animals,  or  chilling  them, 
or  modifying  their  metabolism  unfavorably,  as 
by  inducing  artificial  diabetes.  In  such  cases 
animals  succumb  to  the  very  disease  germs 
against  which  when  in  a  normal  healthy  con- 
dition they  are  immune.  We  know  also  that 
through  hunger,  insufficient  nutriment,  and 
disorders  of  metabolism  such  as  diabetes, 


THE   CAUSE   OF   INFECTIOUS   DISEASE.        267 

human  beings  are  rendered  more  easily  suscep- 
tible to  infection  than  when  in  a  sound  and 
normal  condition.  Before  the  days  of  anti- 
septics the  "  healthy  skin  "  played  an  impor- 
tant part  in  the  progress  of  a  wound. 

The  "  specific  "  qualities  of  disease  germs, 
qualities  which  they  possess  as  do  all  living 
things  adapted  or  adapting  themselves  to  def- 
inite conditions  of  life,  can  only  become  mani- 
fest in  the  shape  of  a  specific  infectious  disease 
when  the  forms  of  motion  which  they  impart 
in  order  to  overcome  the  resistances  arising 
from  the  organization  of  the  human  body  hap- 
pen to  accord  with  the  possibilities  of  motion 
which  occur  in  the  structure  of  man  as  the  re- 
sult of  inheritance  and  adaptation.  Only  in 
this  way  is  it  possible  to  account  for  the  fact 
that — as  has  been  proved  concerning  some 
moulds — micro-organisms  which,  so  far  as  we 
know,  occur  only  as  saprophytes  upon  dead 
material  are  able  to  produce  disease  when  for 
the  first  time, — thus  excluding  any  possibility 
of  an  adaptation, — they  are  artificially  inoc- 
ulated into  susceptible  animals. 

If  the  facts  are  considered  in  a  scientific  spirit, 
rigorously  and  without  prepossession,  it  is  seen 
that  the  sum  of  the  qualities  of  a  disease  germ 
is  only  apparently  the  "  essence  "  of  an  infec- 
tious disease,  that  in  reality,  here  as  elsewhere, 


268  BACTERIOLOGY. 

a  true  internal  cause  is  to  be  found,  inherent 
in  the  internal  organization  of  man.  Just  as 
in  all  natural  processes  without  exception,  so 
here,  the  disease  germs  act  as  liberating  im- 
pulses and  are  able  to  set  free  only  what  in  the 
form  of  a  predisposition  toward  disease  is  in 
some  way  prefigured  both  in  nature  and  amount 
in  the  human  body. 

The  dependence  of  either  resistance  to  or  dis- 
position to  disease  upon  the  conditions  of  life, 
as  well  as  a  like  dependence  of  the  disease 
germs  upon  their  own  conditions  of  existence — 
inasmuch  as  they  likewise  are  living  organisms 
— explains,  without  recourse  to  violent  assump- 
tions, such  facts  as  that  insignificant,  local,  in- 
fectious diseases  may  become  world-wide,as  chol- 
era has  become  in  our  own  century,  that  new 
infectious  diseases  may  make  their  appearance, 
as  for  instance  cerebro-spinal  meningitis  in 
the  last  hundred  years,  and  that  diseases  once 
widely  spread  like  leprosy  and  the  bubonic 
plague  may  dwindle  almost  to  the  vanishing 
point.  We  can  easily  understand  the  fact  also 
that,  even  under  conditions  originally  very  dif- 
ferent, similar  cultural  influences  arising  from 
similar  unsanitary  social  conditions  lead  every- 
where to  the  same  danger  from  diseases  such 
as  tuberculosis,  for  the  reason  that  such  condi- 


THE   CAUSE   OF   INFECTIOUS   DISEASE.         269 

tions  create  a  larger  number  of  the  same  or 
similar  dispositions  toward  disease. 

That  the  "  specificity  "  of  the  disease  germs 
is  a  phenomenon  of  adaptation,  and  hence  not 
an  essence  is  manifest  also  from  the  fact  that 
the  parasites  adapt  themselves  to  given  condi- 
tions of  life  not  only  in  their  mode  of  action 
but  in  their  form.  Koch  has  shown  that  the 
anthrax  bacteria  develop  their  characteristic 
form  of  rods  only  in  their  parasitic  phase.  The 
tubercle  bacilli  have  such  a  strongly  marked 
capacity  of  adaptation  that  Maffucci  and  Koch 
even  distinguished  as  separate  species  or  vari- 
eties the  germs  of  mammalian  and  avian  tu- 
berculosis. Fischel  and  Hueppe,  however,  by 
the  choice  of  suitable  parasitic  and  saprophy  tic 
conditions  of  life  succeeded  in  converting  each 
kind,  one  into  the  other,  and  thus  in  proving 
that  it  is  the  similarity  or  difference  in  condi- 
tions which  ultimately  brings  about  the  great 
divergence. 

Finally,,  in  other  cases  of  which  accurate 
studies  were  made  long  since,  especially  among 
the  higher  animal  and  plant  parasites,  a  close 
adaptation  to  the  conditions  of  life  is  manifested 
in  the  fact  that  a  parasite,  in  order  to  complete 
its  development,  needs  not  only  an  interchange 
of  parasitic  and  saprophytic  modes  of  life,  like 
the  facultative  parasites  among  bacteria,  but 


2/0  BACTERIOLOGY. 

requires  a  complete  and  more  or  less  extensive 
alternation  of  generations.  Such  a  parasite,  in 
other  words,  attacks  different  animals  and 
plants,  one  after  another,  in  each  of  which  it 
passes  through  a  definite  stage  of  development. 
Among  most  parasites  there  occurs  a  free  or 
saprophytic  stage  which  is  advantageous  to 
the  maintenance  of  the  species.  In  such  a 
case  the  parasite  is  often  autoecious,  that  is,  no 
change  of  host  occurs.  In  alternation  of  gen- 
erations there  is  always  change  of  host  or 
hetercecism,  so  that  in  the  extreme  cases  of 
strongly  obligatory  parasitism  this  occurs  in 
a  fashion  as  if  saprophytism  were  altogether 
omitted.  In  the  tape-worm,  for  example,  we 
know  no  free  stage  ;  the  eggs  pass  into  the 
outer  world  but  do  not  develop  (at  least  up  to 
the  present  nothing  of  the  sort  is  known).  The 
scolex  of  Tcznia  solium  is  found  in  hogs,  the 
tape-worm  in  man  ;  the  scolex  of  Tcznia 
mediocanellata  is  found  in  cattle,  the  tape- 
worm belonging  to  it  in  man  ;  the  Echinococci 
are  found  in  man,  the  respective  tape- worm  in 
dogs.  The  scolex  of  Bothriocephalus  latus  is 
found  in  predaceous  fishes,  and  the  tape-worm 
in  man,  but  free  living  embryos  arise  from  the 
eggs  in  water.  In  this  latter  case,  therefore, 
a  limited  free  stage  does  occur.  In  Distomum 


THE   CAUSE   OF   INFECTIOUS   DISEASE. 

hepaticum  three  parasitic  and  two  free  stages 
are  known. 

We  know  that  among  the  rusts  or  Uredinecz 
there  occur  upon  grain  both  summer  spores  or 
uredospores  (stylospores),  and  winter  spores  or 
teleutospores  ;  out  of  the  latter  are  formed  sap- 
rophytically  on  the  fallen  leaves  a  promy- 
celium  which  develops  sporidia  ;  these  sporidia 
get  lodgment  upon  the  barberry  leaf  in  which 
the  aecidia  develop  and  form  besides  spermo- 
gonia,  the  so-called  spermatia.  We  have  there- 
fore three  or  four  parasitic  forms  and  one  free 
form.  Among  the  smuts  or  Ustilaginea  the 
mycelium  develops  spore-bearing  filaments 
upon  the  grain  ;  out  of  these  spores  a  promy- 
celium  with  sporidia  is  formed  saprophytic- 
ally  ;  the  sporidia  may  invade  young  plants 
and  so  begin  again  the  parasitic  cycle,  but  they 
are  able  also  to  vegetate  saprophytically  for 
countless  generations  in  a  torula  form.  Here 
two  saprophytic  forms  and  one  parasitic  form 
are  able  to  exist.  The  spores  of  most  vege- 
table parasites  are  able  to  develop  either  a  sap- 
rophytic form  or  another  parasitic  form. 

An  alternation  of  generations  of  just  this 
kind  has  not  yet  been  demonstrated  among  dis- 
ease-producing bacteria  and  other  microbes,  but 
with  some  species  its  existence  is  not  wholly 
improbable.  It  is  obvious  that  such  complica- 


2/2  BACTERIOLOGY. 

tions  increase  the  difficulty  of  research,  already 
arduous,  but  the  fundamental  facts  that  have 
been  discussed  are  not  thereby  affected  or  in 
any  way  altered.  The  body  of  a  living  organ- 
ism offers  relatively  constant  conditions,  and 
that  explains  why,  in  spite  of  the  complexity 
due  to  an  alternation  of  generations  in  several 
hosts,  the  parasites  can  remain  relatively  the 
same. 

Infection  and  Contagion. 

I  cannot  conclude  my  examination  into  the 
causes  of  infectious  disease  without  referring 
to  still  another  feature  of  the  external  condi- 
tions which  may  be  very  important  practically. 
Granting  the  existence  of  a  given  disposition 
toward  disease,  disease  germs  can  evidently 
afford  opportunity  for  the  manifestation  of 
this  disposition  only  when  they  come  in  con- 
tact with  it.  That  is  the  broad  meaning  of 
the  word  infection.  From  this  point  of  view, 
accordingly,  an  unsuitable  condition  of  the 
general  surroundings  of  life,  such  as  air, 
water,  soil,  and  kind  of  nourishment,  may  be 
of  importance  by  virtue  of  being  the  means 
by  which  the  disease  germ  is  first  introduced 
into  the  body.  The  quite  various  channels  of  the 
mouth,  the  lungs,  and  the  skin  are  available 
for  entrance.  The  organs  affected  in  an  in- 


THE   CAUSE   OF   INFECTIOUS   DISEASE.        2/3 

fectious  disease  are  sometimes  in  the  place 
where  the  disease  germ  enters,  sometimes  in 
tissues  remote  but  more  disposed  toward  the 
disease ;  the  expression  locus  minima  resis- 
tentice  is  used  to  denote  this  latter  relation. 

From  this  standpoint  we  classify  those  dis- 
eases as  contagious  which  can  be  directly  com- 
municated by  mere  contact  with  the  sick  and 
do  not  need  a  go-between ;  and  as  miasmatic 
or  non-contagious  those  which  are  not  trans- 
mitted directly  from  the  sick  but  are  caused  by 
external  agents.  In  the  great  majority  of  in- 
fectious diseases  both  possibilities  of  communi- 
cation exist ;  one  or  the  other  is  the  more  usual 
merely.  In  this  sense  malaria  is  never  natu- 
rally contagious,  but  may  be  artificially  com- 
municated by  transfusion  of  blood  ;  cholera  is 
generally  not  contagious  ;  small-pox  is  always 
contagious.  The  concept  contagion  is  accord- 
ingly used  in  a  narrower  sense  than  that  of 
infection,  and  if  we  depart  from  this  general 
usage  we  must  always  declare  the  fact  and 
make  it  abundantly  evident.  I  say  this  ex- 
pressly because  certain  bacteriologists  use  the 
term  contagion  to  express  the  same  conception 
as  that  implied  in  the  term  infection  or  wound 
infection.  If  this  is  done  in  the  face  of  usage, 
of  the  clinical  experience  of  physicians  and  of 

the  experience  of  every  layman,  then  naturally 
18 


274  BACTERIOLOGY. 

all  diseases  must  be  called  contagious,  for  the 
word  used  in  this  fashion  loses  completely  its 
peculiar  and  narrower  significance.  By  some 
such  quibble,  for  example,  Koch  and  certain 
of  his  followers  are  able  to  declare  cholera  to 
be  a  contagious  disease,  while  medical  expe- 
rience as  well  as  bacteriological  experiments 
prove  plainly  that  cholera  as  a  rule  is  not  in 
the  strict  sense  a  contagious  disease. 


CHAPTER  V. 

CAN   DISEASE   BE   CURED    BY    COMBATING    THE 
CAUSE  ? 

IN  the  preceding  chapter  I  have  attempted 
to  show  what  it  is  that  we  understand  scienti- 
fically by  the  expression,  the  cause  of  disease. 
I  would  lay  especial  stress  upon  the  idea  that 
disease  is  always  a  process  resulting  from  the 
action  of  a  series  of  factors  of  unequal  value  ; 
these  factors  may  be  pictured  as  acting  in  an 
endless  chain  which  it  is  possible  to  break 
asunder  at  any  point.  If  a  link  be  missing  at 
any  point  the  closing  of  the  chain  is  made 
impossible, — the  disease  cannot  be  'brought 
about ;  we  are  able  to  avert  the  disease,  which 
is  always  our  first  and  most  important  task. 
Even  if  the  chain  be  already  closed,  the  dis- 
ease already  in  progress,  we  may  still  perhaps 
succeed  in  warding  off  the  full  effect, — in  part- 
ing the  chain  and  curing  the  disease.  It  re- 
sults, however,  from  the  unequal  value  pos- 
sessed by  the  separate  links  of  the  chain  that 
275 


276  BACTERIOLOGY. 

'  these  have  not  the  same  significance  before  the 
closing  of  the  chain  and  afterwards,  and  that 
again  in  the  case  of  different  diseases,  special 
differences  in  the  value  of  individual  links  may 
exist. 

I  choose  this  comparison  in  order  to  make 
clear  at  the  outset  that  there  can  be  no  cura- 
tive schema  applicable  to  all  cases.  The  duty 
of  physicians  is  to  treat  men  suffering  from 
different  diseases,  not  to  treat  the  diseases 
themselves.  Quite  apart  from  the  psycho- 
logical factors  which  in  the  exhilaration  of 
exactness  are  now  generally  too  much  neg- 
lected, it  must  be  acknowledged  that  medicine 
has  for  a  long  time  shrunk  from  all  question- 
ing about  the  causes  of  disease  and  cure. 

The  symptoms  of  disease  were;  to  be  sure, 
considered  after  a  fashion,  and  then  medical 
practice  entered  upon  a  wild  and  many-sided 
activity  which  generally  found  its  outward 
expression  in  prescriptions  of  large  doses  of 
some  drug  for  all  symptoms,  both  great  and 
small.  A  movement  counter  to  this  was  neces- 
sarily provoked.  Hahnemann  used,  for  every 
disease,  only  one  remedy,  without  reference  to 
the  number  and  succession  of  symptoms,  and 
observed  that  better  results  followed  with 
small  quantities  of  the  remedy  than  with  large 
doses.  Then  the  Viennese  school,  which  Hah- 


CURING   BY   COMBATING   THE    CAUSE.          2/7 

nemann  still  dominated,  lapsed  into  giving 
nothing  at  all  to  the  patient,  and  rested  content 
with  observing  the  course  of  the  malady. 
With  this  "  do-nothing  "  method  of  treatment 
the  outcome  was  at  least  as  satisfactory  as  if 
the  patient  had  been  harassed  with  all  sorts  of 
medicine.  On  the  other  hand,  in  certain  cases 
where  physicians  with  their  great  activity, 
their  many  remedies  and  large  doses  of  medi- 
cine had  done  only  harm,  Hahn  and  Priess- 
nitz  achieved  remarkable  cures  by  using  ordi- 
nary water,  a  remedy  everywhere  accessible. 
Men  gradually  learned  again  to  consider  the 
common  substrata  of  life,  such  as  air  and  food, 
in  their  causative  aspect,  and  forty-one  years 
ago  Brehmer  founded  in  Gorbersdorf  a  now 
famous  sanitarium  where  he  adduced  strong 
proof  in  opposition  to  the  conclusions  of  medi- 
cal empiricism  of  thousands  of  years,  that  the 
dreaded  disease,  lung  consumption  or  tuber- 
culosis, is  curable  by  hygienic  measures. 
Forty-eight  years  ago  Semmelweiss  taught 
that  the  terrible  malady  known  as  puerperal 
fever  which  exceeds  in  fatality  even  small-pox 
and  cholera,  could  be  prevented  by  simple 
cleanliness.  These  instances,  together  with 
Jenner's  successful  combating  of  the  much 
dreaded  small-pox  by  means  of  inoculation 
with  harmless  cow-pox  virus,  constitute  good 


278  BACTERIOLOGY. 

reasons  for  the  change  of  view  that  has  come 
about.  It  is  evident  from  our  exposition  of 
the  causes  of  disease  that  there  is  no  special 
"  vital  force  "  and  no  peculiar  "  healing  power 
of  nature."  In  healing  processes  as  well  as 
in  disease  processes  we  have  to  deal  with  things 
that  are  both  natural  and  comprehensible. 

What,  for  instance,  is  meant  by  the  cure 
of  a  disease  ?  There  are  very  different  things 
which  may  lay  claim  to  this  title.  The  cure  of 
tuberculosis  by  Brehmer's  method  convinces 
us  that  we  can  actually  cure  certain  diseases 
by  utilizing  those  phenomena  which  in  the 
preceding  chapter  I  have  instanced  as  con- 
ditions that  nature  herself  furnishes  in  order 
to  convert  a  given  predisposition  toward  dis- 
ease into  its  opposite,  immunity.  'This  method 
makes  use  of  external  factors  such  as  air, 
water  and  food  to  influence  the  organization 
of  man  and  does  not  concern  itself  at  all  with 
the  disease  germs,  the  tubercle  bacteria.  The 
human  organism  is  treated  with  no  remedy,  no 
foreign  substance.  Both  prevention  and  cure 
of  the  disease  are  attained  by  use  of  the  same 
hygienic  factors.  Through  this  method  the 
natural  forces  of  the  organism  are  strengthened 
and  the  organism  itself  made  capable  of  deal- 
ing with  its  minute  invaders.  The  method 
produces  its  effect  also  by  increasing,  so  to 


CURING   BY   COMBATING    THE   CAUSE.         279 

speak,  the  resistance  to  any  pathological  dis- 
charges of  energy. 

A  cure  of  another  sort  is  seen  when  we  suc- 
cessfully combat  malaria  with  quinine.  Here 
we  introduce  into  the  organism  a  substance 
which  in  certain  quantities  is  a  poison  :  we 
cast  out  the  devil  by  the  aid  of  Beelzebub ;  we 
take  the  risk  that  perhaps  we  may  be  intro- 
ducing so  much  poison  into  the  body  that  a 
disease  due  to  the  drug  will  result.  The  same 
thing  is  true  when  we  treat  syphilis  success- 
fully with  mercury,  or  rheumatism  with  the  sali- 
cylicates.  Indeed  the  reproach  of  the  homoeo- 
pathist  is  that  with  the  ordinary  large  doses  pf 
medicine  that  are  given,  we  do  not  effect  a  cure 
but  merely  increase  the  suffering  of  the  patient 
by  superinducing  a  disease  due  to  the  drug. 
It  is,  however,  noteworthy  that  under  such 
treatment  malaria  patients  do  get  free  from 
malaria  and  become  perfectly  well,  and  that 
the  rheumatic  patient  gets  rid  of  his  painful 
joints  and  swellings  and  is  able  then  calmty 
to  discard  his  salicylicates.  There  must  ob- 
viously be  something  wrong  with  the  homceo- 
pathist's  explanation. 

When  bodies  like  quinine  or  the  salicylicates 
are  used  in  this  way,  it  is  at  once  assumed  by 
some  that  such  substances  act  antiseptically, 
and  that  their  efficiency  in  the  body  is  due  to  the 


280  .  BACTERIOLOGY. 

fact  that  they  destroy  the  parasites,  that  they 
bring  about  an  internal  disinfection,  so  to  speak. 
We  know,  however,  that  antiseptics  and  disin- 
fectants in  general  are  more  powerful  poisons 
towards  the  sensitive  body  cells  than  towards 
parasitic  microbes  like  those  that  provoke  dis- 
ease. We  can  speak  of  a  true  internal  disin- 
fection, accordingly,  only  when  certain  sub- 
stances bear  closer  chemical  relations  to  cer- 
tain parasites  than  to  the  cells  of  the  body, 
when,  in  a  word,  they  act  "  specifically."  It 
is,  in  fact,  the  opinion  of  physicians  that  quin- 
ine and  the  salicylicates  are  "  specific  "  cura- 
tives. Quinine  is  supposed,  according  to  Binz, 
Behring  and  some  others,  to  destroy  or  paralyze 
the  "  specific  "  germs  of  malaria  which  ensconce 
themselves  in  the  red  blood-corpuscles  in  the 
body.  This  view  is  based  upon  the  experi- 
mental demonstration  that  quinine  paralyzes 
these  parasites  in  a  drop  of  blood  ;  the  other 
fact,  that  quinine  paralyzes  also  the  susceptible 
body  cells,  the  white  blood  corpuscles,  is  often 
not  sufficiently  taken  into  consideration,  and 
just  as  little  is  the  fact  regarded  that  in  such 
quantities  as  are  used  in  these  experiments 
quinine  kills  other  microbes  also.  Quinine  is 
an  excellent  disinfectant  for  bacteria  in  the 
vegetative  stage  and  especially  for  many  dif- 
ferent kinds  of  pathogenic  microbes.  In  a  con- 


CURING   BY    COMBATING    THE    CAUSE.          28 1 

centration  of  i  :  500-800  it  checks  the  move- 
ments not  only  of  malarial  parasites,  but  also, 
according  to  Koch,  hinders  the  development  of 
anthrax  bacilli,  and  according  to  Moczutkow- 
sky,  that  of  the  spirillum  of  relapsing  fever, 
notwithstanding  the  fact  that  it  does  not  pos- 
sess the  same  specific  effect  when  administered 
in  these  latter  diseases  as  in  malaria.  It  must 
be  kept  in  mind  also  that  the  amount  of  quin- 
ine which  must  be  added  to  a  drop  of  blood  in 
order  to  destroy  the  malarial  parasite  has  no 
special  bearing  upon  the  cure  of  malarial  fever. 
The  cure  of  malaria  in  man,  even  when  large 
doses  of  quinine  are  given,  is  accomplished  with 
a  quantity  of  the  drug  so  slight  that  in  experi- 
ment it  is  not  sufficient  to  bring  about  the 
paralysis  or  death  of  the  disease  germ. 

The  question  may  well  be  asked,  therefore, 
whether  quinine  is  not  efficacious  in  quite  a 
different  way  from  that  commonly  supposed, 
since  it  neither  paralyzes  nor  kills  the  parasite. 
The  latter  effect  would  demand  relatively  large 
quantities  ;  the  cure  of  malaria  can  be  brought 
about  by  small  quantities.  Now  we  know  that 
small  quantities  of  a  chemical  substance  can 
act  in  a  very  different  way  from  large  quan- 
tities. Paracelsus  long  ago  supposed  that 
curatives — arcana,  he  called  them — include 
substances  that  destroy  the  "  seed  "  of  disease, 


282  BACTERIOLOGY. 

and  others  that  awaken  the  "  healing  power  " 
of  nature.  Capable  physicians,  like  Van  Swie- 
ten,  Brown  and  others,  recognized  after  him 
that  the  action  of  small  doses  differs  from  that 
of  large  doses  of  the  same  drug  ;  opium  for  in- 
stance soothes  in  large  doses  and  stimulates  in 
small.  This  important  empirical  fact  was  for 
a  time  almost  wholly  lost  sight  of,  and  only  the 
significance  of  large  doses  was  appreciated, 
until  Hahnemann  attracted  attention  again  to 
the  value  of  small  doses.  Even  the  childish 
extravagance  which  found  vent  in  homeopathy 
could  not  .impair  the  sound  kernel  of  truth 
which  the  doctrine  contained.  In  more  recent 
times  accurate  investigation  along  this  line  has 
again  been  carried  on  by  Nothnagel,  H.  Schulz 
and  Hueppe.  It  is  now  evident  that  we  have 
not  to  deal  with  any  mystical  "  potentializa- 
tion,"  with  the  supposed  fact  that  a  remedy  be- 
comes more  potent  the  more  it  is  diluted,  but 
with  a  fundamental  biological  law  (cf.  p.  90) 
which  Arndt,  H.  Schulz  and  Hueppe  first  ex- 
pressed as  follows  :  Every  substance  which  can 
paralyze  or  kill  any  cell  or  cell  protoplasm  can 
also  act  in  small  quantities  (on  the  other  side 
of  an  indifferent  point),  as  a  stimulus  to  cell 
activity.  The  absolute  quantities  leading  to 
such  effects  are  very  different  with  different 
substances. 


CURING   BY   COMBATING   THE    CAUSE.          283 

From  a  consideration  of  this  law,  to  which 
there  is  no  exception,  and  because  of  a  recog- 
nition of  the  important  fact  that  when  the  cure 
of  malaria  is  brought  about  with  so-called  large 
doses  of  quinine  the  substance  is  actually  pres- 
ent in  the  blood  in  smaller  amount  than  is 
requisite  for  the  paralysis  or  destruction  of  the 
malarial  parasite,  some  investigators  have  come 
to  the  conclusion  that  quinine  cures  because 
the  small  doses  stimulate  the  cells  of  the  human 
body — perhaps  those  of  the  blood — and  thus 
effect  a  "  specific  "  counteraction.  Over  against 
the  mystical  idea  of  a  "  specific  "  stimulus  it 
is  to  be  always  remembered  that  particular 
stimuli  are  also  general  protoplasmic  stimuli. 
Under  some  circumstances  it  must  happen  that 
not  the  desired  stimulation  of  the  body-cells 
will  take  place,  but  that  instead  the  parasitic 
cells  will  be  stimulated  and  consequent  harm 
result.  There  are  indeed  cases  of  malaria  in 
which  quinine  is  injurious  even  in  large  doses, 
and  Steudel  and  Kiichel  are  of  opinion  that 
sometimes  malarial  cases  may  be  directly  pre- 
cipitated by  small  or  medium  doses  of  quinine  ; 
in  latent  malaria,  that  is,  the  quinine  given  as 
a  preventive  acts  as  a  stimulus  to  the  parasites.' 
The  latter  thereupon  react  to  the  stimulus  and 
provoke  a  case  of  fever,  the  quantity  of  quinine 
present  in  the  blood  being  all  the  time  insuf- 


284  BACTERIOLOGY. 

ficient  to  destroy  or  harm  the  germs.  In  such 
cases,  however,  quinine  is  given  only  prophy- 
lactically  and  therefore  only  in  small  doses  ; 
so-called  large  doses  may  act  in  just  the  same 
way. 

If  proper  quantities  be  selected  the  stimula- 
tive effect  of  small  doses  must,  theoretically  at 
least,  be  brought  into  play  without  any  such 
poisonous  effects  as  might  possibly  follow  from 
larger  doses.  The  cure  is  consummated  with- 
out poisoning,  without  causing  a  drug  disease ; 
it  is  effected  by  the  intervention  of  the  body 
cells.  The  remedy  heals  simply  because  it 
acts  as  a  stimulus  and  temporarily  exalts  the 
natural  forces  of  the  organism.  Since  some 
cases  of  malaria  may  be  cured  by  simple  treat- 
ment with  water,  it  follows  that  the  malarial 
parasite  as  well  as  some  others  can  be  suc- 
cessfully combated  by  a  more  simple  method  of 
stimulating  and  strengthening  the  body-cells. 

If  the  cells  of  the  human  body  are  affected 
more  seriously  and  in  larger  numbers  by  some 
very  severe  attack,  then  stronger  stimuli,  that 
is  to  say  larger  amounts  of  the  drug,  are 
needed.  In  such  cases  the  poisonous  action 
of  the  drug  usually  becomes  manifest  also,  or 
it  may  happen  that  the  stimulus  fails  to  act 
because  it  is  applied  too  late  and  is  hence 
unable  to  affect  many  points.  The  full  util- 


CURING   BY    COMBATING   THE   CAUSE.          285 

ization  of  simple  non-poisonous  means  of  cure 
needs  therefore  the  use  of  only  small  quanti- 
ties of  any  remedy  and  consequently  necessi- 
tates that  treatment  should  be  applied  as  soon 
as  possible.  The  same  is  true  of  every  causal 
method  of  healing  disease. 

The  "  specificity  "  of  curation  by  means  of  a 
chemical  substance  may  be  due  to  the  fact  that 
such  a  substance  acts  as  a  disinfectant  only 
upon  certain  "  species  "  of  microbes  or  parasites, 
or  it  may  lie  in  the  fact  that  such  a  substance 
acts  as  a  stimulus  upon  certain  body-cells  of 
the  human  organism.  After  what  I  have  set 
forth  in  the  preceding  chapter  I  need  hardly 
explain  that  I  use  the  word  "  specific  "  in  this 
sense  only  in  a  very  general  way  in  order  to 
express  any  degree  whatsoever  of  close  relation- 
ship between  substance  and  cell.  There  can 
here  be  no  question  of  a  strongly  specific  action 
in  the  dynamic  sense,  of  an  interchange  be- 
tween molecule  and  molecule.  Chemical  sub- 
stances therefore,  that  act  antiseptically  and 
"  specifically  "  upon  parasites  may  be  able  to 
exert  such  an  action  not  merely  upon  a  single 
species  of  parasite  ;  nor  have  we  cause  to  sup- 
pose that  they  act  as  a  stimulus  to  only  a  sin- 
gle set  of  body  cells.  At  times  indeed  "  speci- 
fic "  substances  may  even  exert  a  harmful 
action  when  given  in  the  "  specific  "  disease. 


286  BACTERIOLOGY. 

If  we  keep  this  fact  always  before  our  eyes 
and  do  not  fall  straightway  into  the  pit  of 
specificity,  as  of  late  unfortunately  many  phy- 
sicians (and  among  bacteriologists  Behring) 
have  done,  the  idea  of  a  "  specific  "  curative 
can  do  no  harm,  since  by  the  expression  we 
mean  merely  a  closer  degree  of  mutual  rela- 
tionship and  use  it  simply  as  a  convenient 
paraphrase. 

From  clinical  and  experimental  evidence  I 
draw  simply  the  following  conclusion  :  there 
are  chemical  substances  that  can  cure  disease. 
We  need  not  abandon  the  hope  of  finding  new 
substances  which,  in  this  strictly  limited 
sense,  act  "  specifically, "  and  we  may  at  least 
cherish  the  hope  that  such  remedies  will  re- 
move the  cause  of  disease  not  by  their  poison- 
ous action,  that  is  by  killing  bacteria  and  other 
parasites,  but  by  acting  as  stimuli  to  the  cells 
of  the  human  organism  and  effecting  a  cure 
by  "  specifically "  stimulating  the  cells  set 
apart  for  defence. 

In  those  diseases  due  primarily  to  the  toxic 
action  of  bacteria  the  poison  formed  might 
presumably  be  rendered  harmless  by  means 
of  antidotes  or  innocuous  remedies  which  serve 
either  to  paralyze  or  neutralize  or  hinder  the 
action  of  the  poison.  The  occurrence  of  a  true 
neutralization  of  organic  poisons  of  the  kind 


CURING    BY    COMBATING   THE    CAUSE.          287 

under  consideration  has,  however,  up  to  the 
present  not  been  proved  ;  on  the  other  hand 
an  antidotal  action,  exerted  within  certain 
limits  is  known  to  occur,  as  when,  for  ex- 
ample, we  counteract  the  effect  of  a  poison 
that  excites  the  nervous  system  by  one  of 
those  poisons  which  depress  nervous  activity 
and  in  larger  quantities  paralyze  it.  The 
counteraction,  like  the  poisonous  action  itself, 
is  effected  through  the  intervention  of  the 
body-cells.  It  does  not,  however,  appear  al- 
together impossible  to  combat  even  the  toxins 
of  infectious  disease  with  chemical  antidotes 
or  indifferent  chemical  substances,  if  we  only 
free  ourselves  from  unchemical  notions  about 
"  specificuy." 

The  scientific  physician  is  plainly  bound  to 
take  into  consideration  everything  pertinent 
to  the  subject,  and  must  not  allow  himself 
to  be  misled  by  forms  of  expression.  If  on  one 
day  there  is  general  agreement  among  physi- 
cians to  prescribe  no  medicine,  on  the  next 
the  disciples  of  the  same  school  are  sure  to 
assail  the  orthodox  physician  with  the  re- 
proach that  there  was  a  time  when  he  did  not 
know  that  healing  substances  occur  in  the 
juice  of  many  plants.  Chemistry  is  now  able 
to  separate  the  important  principles  of  these 
juices  from  the  unimportant,  those  with  heal- 


288  BACTERIOLOGY. 

ing  properties  from  those  with  none,  and  to 
produce  new  substances  among  which  curative 
bodies  are  to  be  found.  If  in  these  investiga- 
tions the  deplorable  error  of  polypragmaty,  or 
great  activity  in  prescriptions,  is  avoided,  and 
science  and  medicine  are  allowed  time  for  test- 
ing the  value  of  these  chemical  substances, 
then  certainly  nothing  can  be  said  against  the 
search  for  "  specific  curatives  "  of  disease. 
Unfortunately  many  errors  have  been  caused 
in  these  latter  days  by  a  superfluity  of  recom- 
mendations of  untried,  really  valueless  and 
often  dangerous  remedies,  the  announcements 
of  which  are  a  source  of  ridicule  to  many 
clinics.  Such  excesses  should  not,  how- 
ever, blind  us  to  the  theoretically  sound  basis 
for  investigations  of  this  sort,,  namely,  that 
chemical  substances  may  be  produced  analy- 
tically or  synthetically  which  are  available  as 
curatives  or  antiseptics  against  disease.  The 
real  foundation  for  such  a  belief  is  easily  seen 
to  be  the  existence  of  chemical  bodies,  often 
very  complex,  which  present,  by  virtue  of 
their  molecular  composition,  definite  possibil- 
ities of  motion  related  to  analogous  conditions 
in  living  things.  They  impinge  upon  the 
energetical  possibilities  of  these  living  things 
in  such  a  way  as  to  set  free  energy,  whether 
they  do  this  by  acting  as  stimuli  to  the  man 


CURING   BY   COMBATING   THE   CAUSE.         289 

or  as  antiseptics  or  disinfectants  upon  the  par- 
asites. At  present,  many  physicians,  reject- 
ing the  good  together  with  the  bad,  in  their 
condemnation  of  the  extravagances  just  de- 
scribed, would  ban  also  the  sound  scientific 
principle ;  some  of  them  discard  the  use  of 
chemical  substances  altogether,  a  proceeding 
which  as  I  should  like  to  prove  definitely,  has 
gone  too  far. 

Since  it  has  become  clear  lately  that  sur- 
geons, in  spite  of  antisepsis  and  even  in  spite 
of  the  possibility,  as  Bergmann  expressed 
it,  of  disguising  gross  stupidity  under  the 
"  mantle  of  Lister,"  are  beginning  once  more 
to  be  truly  modest  and  that  too  especially  as 
concerns  parasitic  processes  in  the  body,  the 
physician  also  is  being  compelled  to  pay  at- 
tention to  various  auxiliary  factors.  Military 
surgery  estimated  correctly  the  true  import- 
ance of  certain  general  hygienic  factors  of  cure 
such  as  fresh  air  and  good  food  at  a  time  when 
internal  medicine  was  still  far  removed  from 
this  position.  Lately  there  has  been  a  similar 
change  in  the  current.  For  example  it  is 
known  that  in  carcinomatous  and  sarcomatous 
tumors  early  operations  often  prevent  the 
generalization  of  infection  and  so  far  can  effect 
a  cure.  But  it  is  found  also  that  an  operation 
frequently  occasions  a  general  infection  in  cases 
19 


BACTERIOLOGY. 

where  without  interference  the  seat  of  disease 
would  have  remained  localized  and  been  re- 
moved by  nature  itself.  Thus  general  miliary 
tuberculosis  occasionally  follows  operations 
upon  tuberculous  bones  or  joints,  general  septi- 
caemia or  pyaemia  may  follow  operations  upon 
osteomyelitis,  and  a  general  infection  may 
follow  incisions  in  phlegmonous  angina  and 
phlegmon.  In  operations  upon  malignant  car- 
buncle, generalized  anthrax  infection  which 
otherwise  would  not  have  been  forthcoming, 
sometimes  results.  Such  experiments  often 
bring  to  us  a  keen  craving  to  possess,  besides 
the  hygienic  remedies, "  specific  "  remedies,  and 
to  enlarge  again  the  sphere  of  action  of  internal 
medicine,  now  greatly  limited  by  the  surgeon. 
Conformably  to  the  law  regarding  stimulus 
we  may  expect  to  cure  sometimes  without  do- 
ing harm  even  when  we  make  use  of  chemical 
substances.  But  chemicals  often  show  closer 
relationship  to  certain  tissues  or  cells  than  to 
others,  without  our  being  compelled  to  assume 
a  true  specificity,  a  fitting  of  molecule  to 
molecule.  Add  to  this  that  every  stimulus 
acts  more  intensely  upon  an  accessible  tissue 
which  is  already  over-stimulated  and  diseased 
than  upon  the  corresponding  sound  tissues  or 
cells  and  it  will  be  seen  that  for  this  reason 
much  smaller  quantities  of  medicine  are  neces- 


CURING   BY   COMBATING   THE   CAUSE.          29! 

sary  than  when  it  is  a  question  of  killing  para- 
sites in  the  body.  If  a  remedy  acts  etiologic- 
ally,  however,  and  attacks  the  energetical 
relations  obtaining  between  parasite  and  host, 
then  it  must  act  upon  all  phases  and  the 
quantity  must  vary  only  according  to  those 
factors  which  are  manifested  externally  as 
symptoms.  That  is  the  necessary  consequence 
of  a  uniform  conception  of  the  continuity  of 
causes. 

Virchow,  in  the  beginning  of  his  pioneering 
activity,  held  another  conception.  He  regarded 
the  single  phases  of  the  disease  as  "  essences," 
considering  them  from  the  one-sided  point  of 
view  of  the  diseased  cells,  and  held  the  opinion 
that  the  separate  phases  and  symptoms  of  the 
disease  must  be  treated  quite  differently.  It 
is  certainly  interesting  that  Henle,  Virchow's 
greatest  opponent  in  etiology  and  co-creator  of 
the  "  rational  "  therapeutics,  and  who,  again  in 
opposition  to  Virchow,  emphasized  particularly 
the  physiological  factors  involved,  arrived  at 
the  same  symptomatological  position  as  con- 
cerns the  treatment  of  disease.  Virchow  him- 
self has  never  in  recent  times  taken  an  op- 
portunity to  express  himself  unambiguously 
on  this  point,  and  while  his  criticism  of  newly- 
discovered  phenomena  and  of  tendencies  in 
science  has  been  often  dogmatic  and  frequently 


2Q2  BACTERIOLOGY. 

even  captious,  we  can  always  understand  why 
many  younger  physicians  adhere  to  his  mode 
of  expression,  although  it  lies  more  than  a 
generation  behind  us,  and  pay  too  little  heed 
to  that  development  of  pathology  which  has 
taken  place  outside  of  Virchow's  sphere  of 
ideas  or  in  opposition  to  them. 

Proceeding  in  this  w^ay,  Behring  has  lately 
assumed  that  we  can  arrive  at  a  uniform  causal 
method  of  treating  and  curing  disease  only 
by  holding  fast  to  Koch's  view  of  the  "  speci- 
ficity "  of  the  disease  germ,  a  view  already 
exploded.  Such  a  view  of  course  relegates 
Virchow's  cellular  pathology  to  the  back- 
ground. I  hope  to  have  shown  that  the  con- 
sistent development  of  the  doctrine  of  causa- 
tion upon  the  firm  basis  of  cellular  pathology 
leads  to  the  same  conception  as  that  held  by 
Behring,  namely,  that  a  disease  can  be  treated 
in  a  uniform  way  with  one  substance.  By 
this  method  of  treatment  we  interfere  only  with 
one  part  of  the  process  and  trust  to  nature 
herself  to  obstruct  the  further  action  of  the 
disease  stimulus. 

My  conception  is  less  one-sided  than  that  of 
Behring  in  so  far  as  that  I  should  not  like  to 
forget  that  a  successful  treatment  can  in  no 
wise  take  into  account  merely  the  "  specificity  " 
of  the  disease  germ  but  must  consider  above 


CURING   BY   COMBATING   THE   CAUSE.  293 

all  else  the  human  organism.  Not  only  the 
toxin  of  the  disease  germ  but  the  human  or- 
ganism itself  may  be  dealt  with.  Diphtheria, 
for  instance,  may  perhaps  be  treated  causally 
and  the  patient  cured  without  any  reference 
whatever  to  the  bacilli  and  their  poison  ;  this 
indeed  frequently  happens  in  tuberculosis. 
While  Behring  would  level  his  weapon  only 
against  the  diphtheria  toxin,  Loffler,  the  dis- 
coverer of  the  diphtheria  bacilli  and  till  lately 
a  strong  supporter  of  Koch's  dogma  of  "  speci- 
ficity," maintains  that  diphtheria  can  perhaps  be 
cured  by  destroying  the  poison-forming  bacilli. 
To  keep  to  my  introductory  figure,  it  is  pos- 
sible to  consider  disease  as  a  process  which  is 
carried  out  like  movement  in  an  endless  chain. 
Disease  may  be  cured  by  influencing  this  uni- 
form movement  in  a  way  which  is  itself  uni- 
form but  of  varying  intensity.  It  is  possible 
also,  always  proceeding  with  an  eye  to  causa- 
tion, to  aim  at  breaking  the  chain  apart  at  dif- 
ferent points  and  in  that  wray  interrupting  the 
movement. 

If  we  are  dealing  with  slighter  and  more 
local  affections  upon  a  micro-biological  basis, 
as  for  example  certain  catarrhal  or  inflam- 
matory conditions  of  the  eye  or  the  throat,  then 
we  are  able  by  suitable  water  dressing  to  in- 
crease locally  the  natural  defensive  powers  of 


294  BACTERIOLOGY. 

the  organism  which  abide  in  its  body  fluids, 
its  local  tissue  cells  and  wandering  cells,  in 
such  a  way  that  this  simple  physical  remedy 
becomes  a  cure.  If  the  local  affection  is  on 
the  point  of  becoming  general,  as  is  observed 
at  times  in  so-called  catarrhal  or  rheumatic 
processes,  then  we  can  frequently  cut  short  the 
whole  process  by  a  hot  bath.  This  succeeds 
because  such  a  physical  method,  through  the 
intervention  of  the  nerves  and  by  the  raising 
of  the  body  temperature,  incites  to  a  tem- 
porarily increased  activity  the  same  natural 
protective  forces  of  the  body. 

By  the  artificial  alteration  of  those  natural 
conditions  the  significance  of  which  as  curative 
factors  I  have  previously  attempted  to  indicate, 
we  are  able  to  act  more  rapidly,  although  not 
so  durably  upon  the  organization  of  man,  and 
in  such  a  way  as  to  enable  him  to  battle  suc- 
cessfully against  the  germs  of  disease.  As 
with  chemical  remedies,  the  judgment  of  a 
competent  physician  is  necessary  here  also, 
since  such  changes  in  conditions  might  lead 
sometimes  to  an  overtaxing  of  the  organism 
and  thereby  do  harm  instead  of  good.  A 
scientifically  trained  physician  with  hygienic 
notions  and  with  marked  individuality  remains 
always  and  everywhere  the  best  remedy  and 
the  surest  means  of  cure. 


CHAPTER  VI. 

IMMUNITY — PROTECTIVE   INOCULATION- 
CURATIVE    INOCULATION. 

IN  the  preceding  chapter  I  have  shown  how 
it  is  possible  to  prevent  disease  or  even  to  cure 
disease  when  already  in  progress  by  availing 
ourselves  of  the  same  simple  hygienic  factors 
which  nature  herself  employs  to  convert  a  pre- 
disposition to  disease  into  immunity. 

Nature  uses  one  remarkable  method  of  trans- 
forming a  predisposition  to  disease  into  im- 
munity, and  this  method  requires  special  con- 
sideration, since  for  some  time  it  has  been 
utilized  also  as  a  means  of  curing  disease. 
The  patient  who  has  successfully  passed 
through  certain  "  specific"  infectious  diseases 
has  derived  some  positive  gain,  inasmuch  as  he 
appears  protected  or  immunized  against  a  second 
attack  ;  therapeutical  and  medical  interference 
with  disease,  on  the  other  hand,  recognizes  as  its 
highest  aim  the  prevention  of  harm  to  the  pa- 
tient, the  majority  of  cures  being  accompanied 
with  injury.  The  individual  who  has  "  had  " 

295 


296  BACTERIOLOGY. 

certain  specific  diseases  rests  in  perfect  con- 
fidence that  he  will  not  again  contract  the 
disease.  It  is  true,  the  hygienist  must  ac- 
knowledge the  fact  that  this  good  fortune  falls 
to  the  lot  of  only  a  portion  of  those  who  have 
had  the  disease,  and  that  even  this  fraction 
often  gain  it  at  the  expense  of  long  illness, 
loss  of  work  and  other  injurious  consequences. 
From  this  point  of  view  it  is  certainly  prefer- 
able, considering  all  things,  not  to  contract 
infectious  diseases  at  all. 

The  very  old  observation  that  protection 
against  a  disease  may  be  acquired  by  endur- 
ing an  attack  of  that  disease  has  led  some 
mothers  to  adopt  the  practice  of  exposing  their 
healthy  children  to  small-pox,  scarlet  fever  and 
measles,  with  the  expectation  that  the  children 
when  thus  exposed  intentionally  and  artifici- 
ally to  the  infection  will  contract  the  disease 
in  a  milder  form  than  the  more  susceptible 
children  who  have  previously  sickened  in  a 
natural  way,  but  that  the  children  thus  delib- 
erately infected  will  gain  the  same  amount  of 
protection  as  the  others.  Thucydides  recom- 
mended that  those  who  had  recovered  from  the 
plague  at  Athens,  and  had  thereby  acquired 
protection,  should  be  employed  in  the  care  of 
the  sick.  In  India  and  China  the  custom  of 
blowing  into  the  nostrils  dried  and  pulverized 


IMMUNITY.  297 

material  from  small-pox  pustules  was  resorted 
to  for  the  purpose  of  obtaining  protective  in- 
oculation, and,  later,  in  the  Orient,  the  method 
of  inoculating  pustule  scabs  beneath  the  skin 
came  into  vogue.  This  latter  method,  the  so- 
called  practice  of  variolation  was  introduced 
from  Constantinople  into  Western  Europe  by 
Lady  Mary  Wortley  Montague  between  1717 
and  1721.  European  physicians  learned  the 
art  so  well  that  only  an  inconsiderable  propor- 
tion of  those  treated  died  of  the  artificial  small- 
pox inoculation  while  an  enormous  number  of 
men  ordinarily  perished  with  natural  small- 
pox. Those  individuals  who  passed  through 
the  artificially  induced  small-pox  were  almost 
as  well  protected  against  the  disease  as  those 
who  had  at  much  greater  peril  overcome  the 
natural  contagion. 

It  was  observed  at  a  later  date  by  herdsmen 
and  milk-maids  in  both  England  and  Schles- 
wig-Holstein  that  cows  occasionally  developed 
on  the  udder  an  eruption  resembling  small- 
pox, and  that  this  was  communicated  to  the 
persons  engaged  in  milking.  Those  who  had 
been  thus  infected  with  "  original  "  cow-pox, 
which  at  first  was  regarded  as  a  peculiar  dis- 
ease, were  often  protected  just  as  well  during 
epidemics  of  true  small-pox  as  those  who  had 
had  the  small-pox.  These  observations  were 


298  BACTERIOLOGY. 

confirmed  by  Fewster  and  Sutton  in  London 
in  1768.  The  landowner  Jesty  in  1774  first 
intentionally  inoculated  himself  and  his  family 
with  cow-pox  for  the  purpose  of  gaining  pro- 
tection against  small-pox.  A  Holstein  teacher, 
one  Pless,  and  above  all  the  English  surgeon 
Jenner  developed  the  method  systematically. 
They  inoculated  persons  first  with  the  cow-pox, 
then  with  genuine  small-pox,  and  observed 
that  in  these  cases  the  inoculation  with  small- 
pox material  no  longer  produced  any  effect.  In 
order  to  do  away  with  the  danger,  for  danger 
was  never  wholly  absent  since  some  persons 
died  in  consequence  of  the  artificial  small-pox 
inoculation,  and  especially  to  put  a  stop  to  the 
spread  and  maintenance  of  the  small-pox 
contagion  by  these  artificial  -  inoculations, 
Jenner,  after  thirty  years  of  experiment,  intro- 
duced the  practice  of  systematic  inoculation 
with  the  supposedly  independent  virus  of  cow- 
pox.  This  is  the  method  of  vaccination  as 
opposed  to  that  of  variolation.  The  fourteenth 
of  May,  1796,  is  regarded  as  the  day  of  the  first 
official  inoculation  with  vaccine,  and  hence  the 
century  jubilee  of  this  great  hygienic  achieve- 
ment has  been  lately  celebrated.  The  protec- 
tion conferred  by  vaccination  was  not  so  ef- 
fective and  did  not  last  so  long  as  that  afforded 
by  artificially  induced  small-pox  or  by  a  natural 


IMMUNITY.  299 

recovery  from  the  disease,  but  trie  method 
always  protected  many  individuals  and  the 
protection  lasted  for  a  long  time. 

As  far  back  as  1839  Thiele  proved  that  the 
supposedly  peculiar  and  independent  disease 
of  cow-pox  was  nothing  other  than  true  human 
small-pox  which  had  been  so  weakened  by 
passing  through  the  organism  of  the  cow  that 
it  behaved  in  human  inoculations  not  like 
human  small-pox,  but  like  cow-pox.  Ceely  in 
1841  produced  cow-pox  in  cows  by  inoculation 
with  human  small-pox.  A  decade  later  Bol- 
linger  and  Stamm  first  accurately  established 
the  fact  that  there  is  no  separate  disease  of  cow- 
pox  (a  statement  that  must,  to  be  sure,  be  cor- 
rected in  so  far  as  that  vesicular  eruptions 
sometimes  occur  on  the  cow's  udder  which  rep- 
resent a  peculiar  disease  of  bacterial  origin, 
similar  to  the  cow-pox,  but  not  conferring  pro- 
tection against  small-pox).  Stamm  in  his  cita- 
tion of  one  case  drew  attention  to  the  possibil- 
ity that  cow-pox,  in  being  carried  over  to  man, 
might  again  become  malignant  and  indeed 
even  like  the  original  small-pox.  The  very 
practice  of  vaccination  might  keep  small-pox 
alive  in  the  land  and  did  not  tend  to  extinguish 
it,  since  the  human  race  could  not  cope  natur- 
ally with  the  disease  as  it  could  with  the  plague 
and  leprosy.  Since  Stamm  became  eventually 


300  BACTERIOLOGY. 

a  fanatical  opponent  of  vaccination  the  things 
he  really  accomplished  were  disregarded.  His 
work  contained  nevertheless  a  sound  kernel 
which,  together  with  the  facts  previously  dis- 
covered by  Jenner  and  Thiele,  included  many 
things  in  the  way  of  practical  experiment  and 
simple  observation  of  nature.  Later  all  this 
ground  had  to  be  experimentally  won  anew. 

Isopathic  or  Specific  Inoculation  With  Living 
Parasites — Attenuation  of  Disease-producing 
Bacteria. 

This  new  principle  is  connected  with  the 
name  of  Pasteur,  who  in  1880  observed  that 
the  parasites  of  chicken  cholera,  a  malignant 
disease  of  the  domestic  fowl,  related  to  the 
swine-pest,  could  by  artificial  treatment  be 
made  to  suffer  such  loss  of  virulence  that  the 
animals  inoculated  became  affected  only  locally 
and  did  not  experience  a  general  and  fatal  in- 
fection. The  animals  after  being  affected  in 
this  way  only  at  the  place  of  inoculation  could 
subsequently  be  inoculated  with  the  virulent 
parasite  without  fatal  results  ;  they  were  pro- 
tected against  the  disease  by  the  preliminary 
inoculation  with  the  weakened  virus.  In  a 
similar  way,  by  attenuating  various  microbes, 
such  as  the  bacteria  of  anthrax,  of  symptomatic 
anthrax  and  of  swine  erysipelas  the  attempt 


IMMUNITY.  301 

was  made  to  secure  protective  virus  (vaccines, 
lymphs)  which  should  affect  the  animals  but 
slightly  and  yet  protect  them  against  a  subse- 
quent infection  from  either  artificial  or  natural 
sources. 

In  1884  Ferran1  first  protected  guinea-pigs 
against  fatal  doses  of  the  cholera  bacteria  by 
subcutaneous  inoculation  with  the  same  germs. 
After  Gamaleia  had  discovered  a  method  by 
which  comma  bacilli  of  constant  and  high  vir- 
ulence could  be  obtained,  W.  M.  Haffkine  cul- 
tivated two  varieties  of  different  degrees  of 
virulence  and  with  these  he  carried  out  in  In- 
dia in  1893-94  protective  inoculation  against 
cholera,  although  with  slight  success.2 

Diminution  of  the  virulence  of  bacteria  is 
especially  effected  by  cultivation  with  abun- 
dant access  of  air,  at  times  in  connection  with 
access  of  light — conditions  the  significance  of 
which  in  the  removal  of  virulence  has  already 
been  mentioned  on  p.  56, — by  cultivation  at 
high  temperatures  (p.  66),  and  by  the  addition 
of  chemical  substances  (p.  90).  Sometimes  it 
is  advantageous  to  proceed  with  the  attenuation 
in  definite  stages  in  order  to  obtain  virus  of 
different  degrees  of  strength.  In  the  case  of 

1  Compt.  rend,  de  1'Acad.  des  sciences,  CI.,  1885. 

2  At  the  present  date  Haffkine's  results  as  a  whole  must  be  looked 
upon  as  distinctly  encouraging.     E.  O.  J. 


3C2  BACTERIOLOGY. 

anthrax,  for  example,  we  adopt  the  plan  of  in- 
oculating the  animals  first  with  a  weaker  then 
with  a  stronger  virus  and  testing  the  immunity 
thus  obtained  by  inoculation  with  a  fully  viru- 
lent material.  It  was  next  discovered  that 
animals  which,  according  to  Pasteur,  were 
vaccinated  securely  against  wound  anthrax, 
nevertheless,  according  to  Koch,  succumbed  to 
intestinal  anthrax,  and  that  therefore  artificial 
immunization  does  not  always  protect  against 
natural  infection.  Quite  satisfactory  results, 
however,  are  obtained  in  both  anthrax  and 
swine-erysipelas,  and  particularly  in  the  dis- 
ease of  cattle  known  as  symptomatic  anthrax 
in  districts  in  which  the  diseases  in  question 
are  very  prevalent.  In  the  latter  disease  a  pro- 
tective inoculation  is  generally 'made  spores 
weakened  by  steam  being  used  (Kitt).  Accord- 
ing to  the  method  employed  for  attenuation  the 
less  virulent  varieties  may  be  degenerate,  not 
growing  well  in  cultures  ;  or  they  may  have 
simply  become  less  parasitic,  that  is  to  say, 
more  saprophytic,  and  grow  even  more  lustily 
than  the  parasitic  parent  form  (they  may  have 
become,  that  is  to  say,  varieties  or  modifications 
of  species,' such  as  occur  for  instance  in  the 
sweet  and  bitter  almonds,  in  the  hemlocks  with 
or  without  conine,  in  the  cinnamon  trees  with 
or  without  aromatic  bark). 


IMMUNITY.  303 

Another  method  of  attenuation  based  in  this 
case  upon  utilization  of  the  living  animal  body 
was  also  first  used  by  Pasteur.  If  the  bacteria 
of  swine-erysipelas  are  transferred  from  swine, 
in  which  they  possess  a  definite  degree  of  vir- 
ulence, to  pigeons,  and  thence  again  to  fresh 
pigeons,  they  acquire  in  the  course  of  this 
transfer  a  heightening  of  their  virulence.  Con- 
versely, a  diminution  of  virulence  is  brought 
about  by  transfer  from  rabbit  to  rabbit.  By 
use  of  the  bacteria  which  have  become  weak- 
ened in  their  passage  through  the  body  of  the 
rabbit  it  is  possible  to  protect  against  that 
degree  of  virulence  shown  in  spontaneous 
swine-erysipelas  ;  or  it  is  even  possible  to  go  a 
step  farther  and  heighten  the  artificial  im- 
munity so  that  it  protects  against  the  germ 
whose  virulence  has  been  increased  artificially 
by  passage  through  the  body  of  the  pigeon. 

Pasteur  discovered  a  similar  thing  in  rabies. 
The  virus, — from  which  a  definite  microbe  has 
not  yet  been  isolated, — becomes  weaker  (the 
degree  of  virulence  shown  in  rabid  dogs  being 
designated  as  "  street-virus  ")  by  passage 
through  the  ape,  stronger  by  passage  through 
the  rabbit.  Pasteur  made  use  of  the  spinal 
cord  of  rabbits  in  which  virulence  had  been 
exalted  to  the  highest  point,  and  called  this 
strongest  obtainable  virus  "  virus  fixe."  In 


304  BACTERIOLOGY. 

the  production  of  the  desired  degree  of  vir- 
ulence the  spinal  cord  is  dried  in  air  free  from 
water  and  carbonic  acid  ;  by  that  means  the 
virus  is  weakened.  The  duration  of  the  pro- 
cess of  attenuation  determines  the  amount  of 
decrease  in  virulence.  If  animals  are  inocu- 
lated writh  the  weakest  material  and  then  with 
a  slightly  stronger,  and  so  on,  it  becomes  pos- 
sible eventually  to  inoculate  safely  with  the 
fresh  and  most  virulent  cord  of  a  rabbit.  The 
animals  thus  vaccinated  no  longer  die  from 
rabies ;  they  have  even  become  immune  to  a 
more  virulent  rabic  virus  than  is  likely  to 
occur  in  nature. 

In  all  these  cases,  cultures  or  viruses  were 
used  which,  though  attenuated,  were  still  active, 
but  in  1887  Hueppe  discovered  in  the  case  of 
chicken  cholera  and  Wildseuche,  and  Chauveau 
in  1889  in  the  case  of  anthrax  that  even  cul- 
tures altogether  attenuated,  which  had  become 
purely  saprophytic  and  no  longer  excited 
any  sort  of  pathogenic  action  could  never- 
theless confer  immunity  against  virulent  cul- 
tures. 

In  all  the  inoculations  hitherto  described  the 
material  used  in  inoculation,  however  obtained, 
and  whatever  degree  of  attenuation  it  might 
possess,  was  identical  in  kind  with  the  infective 
substance.  Protective  inoculation  would  seem 


IMMUNITY.  305 

from  this  to  be  strictly  "  specific,"  or  still  more 
precisely  expressed,  "  isopathic." 

Still  another  step  was  taken  in  the  same 
direction.  The  experiments  described  above 
were  carried  out  with  living  microbes.  Even 
when  attenuated  cultures  were  used  it  some- 
times happened  that  some  of  the  inoculated  ani- 
mals died  either  through  accidental  inoculation 
of  too  large  amounts  of  material  or  through 
greater  individual  predisposition  to  disease, 
thus  affording  direct  proof  that  attenuated 
material  might,  by  passing  through  suitable 
animals,  again  become  virulent.  The  attempt 
was  made  therefore  to  dispense  altogether  with 
the  living  parasites  and  their  attenuated  modi- 
fications. 

Inoculation  With  Metabolic  Products — Protect- 
ive Substances  and  Poisons — Immunity  Does 
Not  Depend  Upon  Habituation  to  Poison. 
Panum  in  1874  first  established  the  fact  that 
the  poisonous  action  of  bacteria  is  due  to  solu- 
ble poisons  formed  by  the  bacteria,  but  separ- 
able from  them,  and  that  this  poisonous  action 
could  be  advantageously  combated  indirectly, 
namely,  by  combating  the  germs  forming  the 
poison.     It  was  afterwards  discovered  by  Koch 
in   1878,  by  Chauveau  in   1880,  and  later  by 
many  other  observers  that  a  number  of  patho- 
genic germs  actually  injure  the  organism  less 


20 


306  BACTERIOLOGY. 

by  their  proliferation  in  the  body  than  by  the 
formation  of  soluble  poisons,  which  are  ab- 
sorbed, pass  into  the  circulation  and  so  affect 
important  tissues  like  the  nerves,  muscles  or 
glands.  It  was  shown  to  be  possible,  by  sepa- 
rating the  poisons  from  the  bacteria  by  nitra- 
tion or  by  killing  the  bacteria  by  means  of 
chemicals  or  heat,  to  produce  with  these  poisons 
manifestations  of  disease  that  appeared  to 
resemble  those  which  earlier  had  been  pro- 
duced only  with  the  living  bacteria.  These 
poisons  were  at  first,  in  accordance  with 
Brieger's  view,  held  to  be  organic  bases,  the 
so-called  ptomams.  Later  it  was  seen  that  the 
bacterial  poisons  were  poisonous  proteid  bodies 
or  substances  closely  related  to  proteids  or  at 
least  not  positively  separable  from  them,  and 
that  they  often  possessed  properties  similar  to 
those  of  the  digestive  ferments  (p.  125). 

The  French  investigators  Toussaint  and 
Chauveau  as  far  back  as  1880  endeavored  to 
establish  the  theory,  in  opposition  to  Pasteur's 
view,  that  the  protective  effect  resulting  from 
the  incorporation  into  the  body  of  attenuated 
disease  germs  depends  upon  the  fact  that  the 
soluble  metabolic  products  of  the  germs  confer 
immunity.  The  American  investigators  Sal- 
mon and  Smith  finally  proved,  in  1886,  that 
this  is  sometimes  the  case,  by  successfully 


IMMUNITY.  307 

using  poisonous  "  metabolic  products  "  to  pro- 
tect against  the  virulent  disease  called  Ameri- 
can swine-plague.  Such  soluble  substances, 
it  was  hoped,  could  be  measured  accurately 
and  then  safely  introduced  into  the  body  in 
definite  quantities.  With  substances  of  this 
kind,  freed  from  germs  by  heating  or  by  filtra- 
tion, Foa  and  Eonome  produced  immunity 
against  Proteus-,  Charrin  against  Pyocyaneus, 
Roux  and  Chamberland  against  maligant 
oedema,  Roux  against  symptomatic  anthrax, 
Gamaleia  against  the  Vibrio  septicaemia  of 
pigeons  and  against  cholera,  and  C.  Frankel 
against  diphtheria. 

It  might  seem  safe  to  infer  from  these  facts 
that  immunity  consists  in  accustoming  the 
organism  to  the  "  specific  "  poisons  of  the  dis- 
ease germs.  Such  a  conclusion,  however,  is  not 
in  harmony  with  the  observations  previously 
mentioned  as  made  by  me  in  1887  and  by 
Chauveau  in  1889,  for  we  succeeded  by  the  use 
of  entirely  attenuated  bacteria,  which  had  be- 
come wholly  saprophytic  and  no  longer  capable 
of  forming  specific  poisons,  in  producing  im- 
munity towards  these  same  bacteria  in  a  fully 
virulent  condition.  Hueppe  and  Wood  suc- 
ceeded also  in  1889  in  producing  immunity  to- 
wards disease-producing  bacteria  by  inoculation 
with  ordinary  saprophytes  derived  from  water 


308  BACTERIOLOGY. 

and  soil ;  immunity  towards  anthrax  was  ob- 
tained in  this  way  and  the  first  harmless  pro- 
tective inoculation  thereby  effected. 

The  conviction  became  general,  moreover, 
that  many  of  the  methods  employed  to  sepa- 
rate the  "  specific  "  poisons  from  the  parasites 
forming  them  destroyed  or  altered  the  so-called 
"  specific "  poisons,  and  it  was  seen  that 
immunity  was  still  obtained  with  the  metabolic 
products.  In  fact,  if  only  the  poisons  them- 
selves were  introduced,  immunity  did  not  result, 
as  Roger  and  Charrin  discovered  before  in  work- 
ing with  Pyocyaneus,  C.  Frankel  with  diphthe- 
ria, and  Hueppe  with  chicken  cholera.  Guided 
by  these  facts,  Gamaleia  and  Hueppe,  and 
afterwards  H.  Buchner,  were  led  to  the  discov- 
ery that  the  "  specific  "  poisonous  substances 
found  outside  the  parasites  in  the  culture  fluids, 
were  not  identical  with  the  protective  sub- 
stances occurring  in  the  disease  germs  or  their 
metabolic  products. 

By  these  discoveries  along  the  line  of  "  speci- 
fic "  immunization  it  was  established  that:  i, 
Undergoing  the  disease,  2,  Inoculation  with 
attenuated  germs,  3,  Inoculation  with  disease 
germs  which  have  become  wholly  impotent,  4, 
Inoculation  with  saprophytes,  and  5,  Inocu- 
lation with  the  metabolic  products  of  the  para- 
site, can  all  confer  immunity  while  ;  6,  Inocu- 


IMMUNITY.  309 

lation  with  the  specific  poisons  effects  no  im- 
munization. 

It  was  next  proved  by  various  series  of  ex- 
periments that  completely  attenuated  bacteria 
can  not  as  a  matter  of  fact  any  longer  form  the 
"  specific  "  poison.  Following  out  this  clue 
the  attempt  was  made  to  deprive  virulent  cul- 
tures of  their  poison.  The  bacterial  poisons 
have,  as  mentioned  on  p.  124,  the  character  of 
active  proteid  bodies,  and  in  a  moist  condition 
they  are  very  sensitive  to  high  temperatures. 
If  the  fluids  containing  the  poisons  be  warmed 
to  about  55°-65°  they  become  for  the  most  part 
inactive  and  lose  their  poisonous  qualities. 
As  Hueppe  has  discovered  for  chicken  cholera 
and  Asiatic  cholera,  Brieger  and  C.  Frankel 
for  diphtheria,  F.  and  G.  Klemperer  for  pneu- 
monia infection  in  rabbits,  Brieger,  Kitasato 
and  Wassermann  for  cholera,  diphtheria, 
typhoid  fever  and  swine-erysipelas,  immunity 
can  be  obtained  by  the  use  of  cultures  devoid 
of  poison.  The  explanation  of  this  kind  of 
immunity  is  that  the  bacteria  are  prevented 
from  growing  and  forming  their  poisons  in  the 
body  ;  they  are  destroyed  just  as  saprophytes 
are,  and  the  organism  of  man  or  of  the  lower 
animals  is  in  consequence  not  subjected  to  a 
contest  with  the  bacterial  toxins. 

We  are  still  in  the  dark  as  to  the  nature  of 


3iO  BACTERIOLOGY. 

the  protecting  substances.  That  they  are  in- 
tegral elements  of  the  living  protoplasm  of  the 
bacterial  cell  appears  certain  ;  they  are  supposed 
to  possess  a  higher  phosphorus  content  than 
the  toxin,  and  they  pass  with  greater  diffi- 
culty through  porcelain  filters.  We  must  infer 
from  the  protective  action  of  impotent  cultures, 
that  these  substances  are  the  expression  of  the 
more  immutable  qualities  of  the  species,  and 
not,  like  the  poisons,  of  the  variable  character- 
istics. It  may  be  legitimately  conjectured  that 
foreign  protoplasm  and  active  proteid  are  usu- 
ally able  to  confer  some  sort  of  immunity  al- 
though in  varying  degrees  according  to  nature 
and  origin. 

If  experiments  are  made  with  proteid-like 
poisons  of  diverse  origin  (with' the  vegetable 
poisons  abrin  and  ricin,  as  Ehrlich  has  done, 
and  as  Roux,  Behring  and  Tizzoni  have  done 
in  a  similar  way  with  tetanus  and  diphtheria 
poisons),  it  is  seen  that  the  animal  organism 
comports  itself  toward .  these  poisons  just  as 
toward  arsenic,  alcohol,  nicotine  or  morphine. 
The .  organism  accustoms  itself  to  increasing 
quantities  of  the  specific  poison,  and  becomes 
tolerant  of  it,  but  is  not  affected  to  the  ex- 
tent of  acquiring  immunity,  and  is  not,  prop- 
erly speaking,  immunized.  If  true  immunity 
be  obtained  with  "  metabolic  products,"  bodies 


IMMUNITY.  .       311 

must  be  present  in  these  products  which  act 
unlike  the  poisons. 

To  put  it  briefly,  the  protecting  bodies  are 
either  the  bacterial  cells  themselves,  or  they 
exist  in  the  cell-body,  or  they  become  separated 
externally  from  the  cells.  In  the  so-called 
metabolic  products  present  in  culture  fluids 
after  bacterial  growth  are  found  not  only  the 
true  toxins  but  always  along  with  these  the 
dead  bodies  of  the  bacteria,  together  with  the 
dissolved  portions  of  dead  bacteria  and  the  sol- 
uble cell  substances  that  have  separated  from 
the  bacteria  during  life.  In  the  active  culture 
fluids,  not  only  the  poisons,  but  cell  substances 
of  another  kind  are  present  in  solution,  and 
both  of  these  may  be  separated  by  filtration 
from  the  living  or  dead  bacterial  cells.  If  cul- 
ture fluids  in  which  active  parasites  have  grown 
be  heated  to  about  70°  the  "  specific  "  poisons 
are  destroyed  or  changed,  although  at  this  tem- 
perature the  soluble  cell  substances  which 
confer  immunity  appear  to  suffer  no  essential 
alteration.  But  not  only  those  parasites  which 
are  attenuated  and  form  little  poison  and  those 
that  have  become  impotent  and  no  longer  form 
poison,  but  also  certain  harmless  saprophytes 
which  form  no  poison  at  all,  possess  such 
soluble  protective  cell  substances.  It  is  very 
improbable  that  the  protecting  substances  are 


312  BACTERIOLOGY. 

nothing  but  the  poisons  modified  by  heating, 
as  some  investigators  have  asserted.  The 
formation  of  both  protective  substance  and 
poison  appears  to  be  a  "  specific  "  activity  of 
certain  species  of  micro-parasites.  The  at- 
tenuation of  disease-producing  bacteria  depends 
accordingly  upon  the  fact  that  the  capacity  for 
forming  poisons  is  diminished  while  other  cell 
activities  are  not  essentially  influenced. 

Proteids. 

Those  proteid  bodies  which  are  obtained  by 
boiling  bacterial  cultures  with  and  without  ad- 
dition of  potash  lye  or  of  glycerine  are  certainly 
not  the  substances"  that  bestow  protection. 
Whether  the  proteids  obtained  by  this  method 
are  produced  from  the  real  protective  sub- 
stances by  the  high  temperature  is  still  uncer- 
tain. H.  Buchner  discovered  that  such  pro- 
teids provoke  aseptic  fever  and  inflammation, 
and  Hueppe  and  Scholl  found  also  that  they 
act  in  characteristic  ways,  and  cause  leuco- 
cytosis  or  local  suppuration.  Prudden  and 
Hodenpyl  found  that  they  act  as  a  formative 
stimulus  to  the  body  cells  and  Gartner  and 
Romer  that  they  bring  about  lymph  secretion. 
In  this  category  belong  such  substances  as  the 
"  tuberculin  "  obtained  by  Koch  from  tubercle 
bacteria  and  the  "  mallein,"  obtained  from  cul- 


IMMUNITY.  313 

tures  of  the  glanders  bacillus.  These  proteids 
confer  no  specific  immunity  and  no  specific  toler- 
ance of  poison  ;  they  are  neither  the  specific 
protective  substances  nor  the  specific  poisons  of 
the  bacteria.  According  to  Koch  it  is  possible 
to  accustom  the  body  to  the  presence  of  large 
quantities  of  these  proteids.  They  bring  about 
a  reaction  of  the  body  cells  and  tissues  by  excit- 
ing an  inflammation  which  enables  the  organ- 
ism to  defend  itself  from  the  invading  parasites. 
In  rare  cases  a  cure  of  tuberculosis  can  perhaps 
be  effected  by  tuberculin,  but,  as  is  well  known, 
the  expectation  of  a  "  specific  "  cure  has  not 
been  fulfilled.  The  inflammatory  reaction,  with 
the  resulting  increase  of  temperature  which 
follows  the  injection  of  tuberculous  animals 
with  tuberculin  may  reveal  the  existence  of  an 
internal  seat  of  disease.  This  method  of  using 
tuberculin  has  been  widely  introduced  for  the 
diagnosis  of  the  disease  of  cattle  known  as 
"  pearly  disease,"  and  mallein  likewise  is  fre- 
quently used  with  success  to  obtain  an  early 
diagnosis  of  glanders.  It  must  however  be  men- 
tioned that  sometimes  the  reaction  is  not  forth- 
coming, and  other  processes  often  intervene  for 
the  simple  reason  that  the  proteids  are  not  spe- 
cific in  the  ordinary  sense  of  the  word.  Indeed, 
according  to  Weichselbaum,  Ortner  and  Klein, 
tuberculin  has  no  effect  at  all  upon  uncompli- 


314  BACTERIOLOGY. 

cated  human  tuberculosis,  but  does  bring  about 
a  reaction  in  the  case  of  mixed  infections  oc- 
curring in  the  form  of  inflammation  of  the 
lungs  by  stimulating  the  pneumonically  infil- 
trated parts.  According  to  Romer  it  is  possible 
to  employ  in  the  place  of  tuberculin  and  also 
of  mallein  the  proteids  produced  by  many  diffe- 
rent kinds  of  bacteria.  Certain  proteids,  there- 
fore, act  as  powerful  stimuli  and  in  such  a  way 
that  active  proteid  bodies  of  a  kind  to  be  men- 
tioned presently,  and  which  are  possessed  of 
bactericidal  and  antitoxic  power,  make  their 
appearance  in  the  blood  in  greater  abundance 
than  before ;  such  proteids  are  not  themselves 
the  specific  protecting  substances. 

In  this  discussion  it  is  of  practical  advantage 
to  distinguish  between  natural*  resistance  or 
immunity,  acquired  immunity  (gained  either 
naturally  or  artificially)  and  the  habituation 
to  or  tolerance  of  poison.  In  natural  immunity 
microbes  and  parasites  can  not  invade  the  body 
of  the  organism  ;  the  body  possesses  the  power 
of  destroying  the  parasites  and  their  poisons. 
In  specifically  acquired  immunity  the  body 
has  gained  the  power  of  preventing  the  inva- 
sion of  certain  definite  parasites  and  their  for- 
mation of  poison,  although  before  the  acquisi- 
tion of  this  property  these  germs  were  able  to 
enter  the  body  and  do  harm.  In  a  state  of 


IMMUNITY.  315 

habituation  to  poison  the  body  has  acquired 
merely  the  power  of  "  paralyzing  "  the  specific 
poison,  although  the  parasite  may  perhaps 
still  be  able  to  grow  in  the  t  body  ;  the  latter 
event,  however,  is  no  longer  of  moment  because 
any  poison  formed  is  rendered  innocuous.  In 
both  natural  and  acquired  immunity  the  body 
disposes  of  a  quantity  of  poison  equal  to  that 
formed  in  the  course  of  a  natural  or  artificial 
infection,  while  by  gaining  an  habituation  to 
poison,  the  body  becomes  accustomed  to  very 
much  larger  quantities.  The  body,  then,  may 
acquire  the  power-to  cope  with  poisons,  or  the 
power  naturally  existing  may  be  heightened,  in 
a  manner  differing,  at  least  quantitatively,  from 
that  shown  in  natural  resistance  and  acquired 
immunity  :  for  example,  according  to  Behring, 
an  animal  may  not  be  tolerant  of  tetanus  toxin 
although  displaying  immunity  to  the  disease, 
or,  conversely,  the  animal  may  be  susceptible 
to  the  toxin  at  a  time  when  its  blood-serum  is 
to  the  very  highest  degree  antagonistic  to  it. 
In  hydrophobia  both  the  poisonous  action  and 
the  immunizing  power  are  associated  with  the 
central  nervous  system  and  inoculation  with 
material  from  this  source  can  produce  immunity 
even  when  the  material  no  longer  acts  poison- 
ously.  By  inoculation  with  "  metabolic  pro- 
ducts "  the  body  acquires  immunity  to  the  dis- 


316  BACTERIOLOGY. 

ease  as  well  as  tolerance  of  the  poisons  ;  hence 
stress  must  be  laid  sometimes  upon  one,  some- 
times upon  the  other  process  according  to  the 
mode  of  action  of,  the  parasite. 

In  diseases  such  as  tetanus  and  diphtheria 
which  are  due  less  to  the  multiplication  of 
bacteria  than  to  the  action  of  their  toxins 
it  is  perhaps  better  to  immunize  not  with  at- 
tenuated, but,  according  to  Beh ring's  method, 
with  fully  virulent  or  hyper-virulent  cultures 
since  what  we  endeavor  in  the  first  instance  to 
obtain  by  immunization  is  merely  a  form  of 
habituation  to  poison.  This  method  of  proce- 
dure, however,  is  not  necessary.  As  mentioned 
above,  Frankel  was  able  to  produce  immunity 
against  virulent  diphtheria  bacteria  by  the  use 
of  cultures  deprived  of  their  toxin,  the  expla- 
nation being  simply  that  the  immunized  organ- 
ism, in  preventing  the  growth  of  the  bacteria, 
thereby  prevents  the  formation  of  poison,  so 
that  habituation  to  the  poison  itself  becomes 
'unnecessary. 

Protective  Serum — Active  and  Passive  Immu- 
nity—  Tissue  Immunity  and  Antitoxin  Im- 
munity. 

There  is  still  another  and  entirely  different 
method  of  specific  immunization.  In  1884 
Ferran  used  subcutaneous  injections  of  the 


IMMUNITY.  317 

blood-serum  of  cholera  patients  for  the  pur- 
pose both  of  curing  patients  suffering  with 
cholera  and  of  protecting  healthy  individuals 
from  its  attack,  but  it  is  not  clear  what  his 
theory  of  the  proceeding  was.  Hericourt  and 
Richet  in  1888  inoculated  dogs  with  pyaemia- 
staphylococci,  and  the  dogs  developed  local 
abscesses.  When  the  serum  of  such  dogs,  after 
healing  was  accomplished,  was  conveyed  to 
rabbits — animals  which  otherwise  would  have 
rapidly  succumbed  to  infection  with  the  dis- 
ease— all  of  the  rabbits  were  found  to  be  pro- 
tected, whereas  the  serum  of  healthy  unin- 
oculated  dogs  protected  the  rabbits  only  in  a 
fraction  of  the  cases.  The  serum  of  healthy 
dogs  exerted  a  certain  influence,  but  the  serum 
of  those  dogs  which  had  endured  the  definite 
affection  possessed  much  more  perfectly  the 
power  of  imparting  immunity  to  the  disease. 
The  quantitative  difference  in  this  case  at 
least  was  in  favor  of  the  preliminary  "  specific  " 
immunization. 

Babes  and  Lepp  discovered  in  1889  that  the 
serum  of  dogs  immunized  against  hydropho- 
bia protected  other  dogs  against  the  disease. 
More  important  was  the  discovery  of  Behring 
and  Kitasato  in  1890,  that  the  blood  and  blood- 
serum  of  animals  that  had  been  immunized 
against  tetanus  and  diphtheria  conferred  upon 


3l8  BACTERIOLOGY. 

susceptible  animals  immunity  to  the  diseases 
in  question  and  therefore  apparently  acted 
qualitatively  or  isopathically.  Ehrlich  showed 
that  the  milk  of  immunized  animals  exerted 
the  same  effect.  Immunity  obtained  by  the 
use  of  the  serum  was  somewhat  transient  as 
compared  with  immunity  acquired  by  means 
of  inoculation  with  the  living  parasites  or  their 
metabolic  products,  and  as  compared  with  the 
acquired  habituation  to  poison  :  it  lasted  only 
a  short  time,  but  on  the  other  hand  it  made  its 
appearance  very  quickly.  It  was,  so  to  speak, 
"  passive,"  while  the  other  was  "  active."  This 
difference  between  active  and  passive  immu- 
nity, which  apparently  cannot  be  bridged  over, 
may  be  illustrated  by  the  following  examples  : 
If  sheep  are  endowed  with  an  active  and 
durable  immunity  against  cutaneous  anthrax, 
they  will  nevertheless  succumb  to  intestinal 
anthrax,  as  Koch  has  proved.  If  rabbits  are 
inoculated  with  rabbit  septicaemia  in  one  ear  or 
On  the  cornea  of  one  eye,  a  subsequent  infection 
on  the  same  side  of  the  body  no  longer  takes 
effect ;  but,  according  to  Loffler,  the  animals 
still  succumb  to  infection  of  the  ear  or  cornea 
on  the  other  side,  and  it  is  only  after  some  time 
that  a  general  immunity  of  the  whole  organism 
can  be  remarked.  According  to  Pasteur,  rab- 
bits which  are  protected  against  hydrophobia 


IMMUNITY.  319 

arising  from  skin  infection  or  from  wounds, 
succumb  if  the  virus  be  inoculated  directly 
into  the  brain.  According  to  experiments  by 
Hueppe  and  Salus,  if  fowls  be  inoculated  in  a 
pectoral  muscle  with  the  bacteria  of  chicken 
cholera,  or  pigeons  be  inoculated  in  the  same 
way  with  the  germ  of  human  cholera,  the  birds 
can  not  afterwards  be  successfully  infected  on 
the  same  side  of  the  body,  although  an  infec- 
tion of  the  pectoral  muscle  on  the  other  side 
is  still  effective ;  then  ensues  a  stage  where 
even  this  mode  of  inoculation  no  longer  suc- 
ceeds, but  where  direct  inoculation  into  the 
blood  current  still  suffices  to  cause  death. 
Guinea-pigs  which  have  been  securely  immu- 
nized against  cholera  infection  by  way  of  the 
peritoneum  succumb,  just  as  readily  as  if  noth- 
ing had  happened,  to  infection  through  the 
stomach. 

Protective  inoculation  requires  time,  for  the 
simple  reason  that  the  protective  substances 
must  act  as  liberating  or  exciting  stimuli  upon 
definite  tissue-cells  of  the  body.  This  kind 
of  immunity  is  acquired  only  through  the  in- 
tervention of  the  body-cells  ;  active  immunity 
is  an  immunity  of  cells  or  tissues.  The  same 
thing  holds  good  of  the  habituation  to  or 
tolerance  of  poisons.  "  Active  "  immunity  of 
the  sort  obtained  through  the  influence  of  the 


320  BACTERIOLOGY. 

body-cells,  and,  although  in  somewhat  slighter 
degree,  "  active  "  tolerance  of  poisons,  can  per- 
sist for  months  and  even  for  years,  because 
these  conditions  do  not  depend  upon  the  tran- 
sient bacterial  invasion,  but  upon  the  acquired 
properties  of  the  body-cells.  The  body-cells, 
because  of  their  relatively  great  independence 
of  varying  conditions  of  nutrition,  are  able  to 
cling  to  their  inherited  or  acquired  character- 
istics. For  this  reason  they  render  more  per- 
manent the  qualities  of  the  blood  and  other 
body-fluids  which  maintain  an  interchange  of 
substances  with  them. 

Without  this  intervention  of  the  cells  the 
body-fluids  very  quickly  rid  themselves  of 
foreign  substances  either  by  excretion  through 
intestine,  stomach,  kidneys  or  skin,  or  by  oxi- 
dation or  by  chemical  combination.  New  and 
lasting  characteristics  are  not  acquired  or  pre- 
served by  the  body-fluids  alone.  It  is  the  organ- 
ism of  the  host, — the  cellular  tissue  of  the 
human  being, — that  reacts  towards  the  stim- 
ulus of  those  bacteria  or  bacterial  proteids  or 
toxins  with  which  we  endeavor  to  heighten  the 
resistance  towards  parasites  or  parasitic  poisons. 
Bacteriology  affords  powerful  support  to  cellu- 
lar pathology,  a  fact  that  can  not  be  urged  too 
strongly  against  Behring's  view. 

In  the  case  of  "  passive  "  vaccination,  or  the 


IMMUNITY.  321 

antitoxin-immunity  obtained  with  serum,  ani- 
mals seem  to  be  immunized  so  quickly  that 
any  participation  of  the  body-cells  in  the  pro- 
cess appears  to  be  out  of  the  question.  Pro- 
tective substances  are  apparently  introduced 
directly  with  the  serum  ;  they  must  therefore 
act  almost  immediately,  and  like  all  foreign 
substances  are  also  soon  eliminated.  Let  us 
seek  to  discover  therefore  the  nature  of  these 
hypothetical  substances  that  are  contained  in 
the  protective  serum. 

When  Ehrlich  rendered  animals  immune 
towards  two  proteid-like  poisons  of  vegetable 
origin,  abrin  from  the  jequirity-bean  (Indian 
licorice,  Abrus  prcecatorius]  and  ricin  from  the 
castor-oil  bean,  tolerance  of  these  respective 
poisons  seemed  to  consist  in  the  fact  that  the 
immune  animals  possessed  in  their  serum  a 
kind  of  antidote,  antitoxin,  or  "  anti-substance" 
(Antikbrper]  as  Ehrlich  somewhat  singularly 
expressed  it.  These  substances,  which  are 
themselves  proteid-like,  were  supposed  to  para- 
lyze the  proteid-like  poison,  or,  as  Behring 
conceived,  to  neutralize  it.  The  difference  be- 
tween active  and  passive  immunization,  be- 
tween tissue  immunity  and  antitoxin  immu- 
nity, consists,  then,  in  the  fact  that  in  active 
immunity  the  organism  inoculated  forms  this 
antitoxin  but  slowly  and  with  the  help  of  its 

21 


322  BACTERIOLOGY. 

cells,  which,  however,  can  continue  for  a  long 
time  to  produce  the  antitoxin.  "  Passive  "  im- 
munity differs  in  the  respect  that  these  "  anti- 
substances  "  are  introduced  into  the  body  all 
cut  and  dried,  as  it  were.  In  the  latter  case 
the  animal  treated  with  serum  experiences  the 
benefit  of  the  antidote  without  on  its  side  bear- 
ing any  of  the  burden  of  preparation,  while  the 
animal  alone  that  affords  the  protective  serum 
assumes  actively  the  dangerous  responsibility 
of  forming  the  antidote.  In  passive  immuni- 
zation the  cells  of  the  secondarily  protected  ani- 
mal contribute  nothing  to  the  acquisition  of 
immunity,  and  consequently  the  antidote  in- 
corporated in  its  body  remains  like  a  foreign 
proteid  ;  the  cells  eliminate  this  strange  proteid 
as  quickly  as  possible.  It  is  f6r  this  reason 
that  passive  immunity  is  not  lasting. 

As  Behring's  conception  has  grown  in  favor, 
Ferran's  experiments  upon  cholera  have  been 
unwittingly  taken  up  again ;  immunity 
-against  cholera  has  been  brought  about  by 
the  use  of  the  serum  of  cholera  patients.  G. 
Klemperer,  Lazarus  and  Metschnikoff  found 
that  this  serum,  varying  it  is  true  in  an  extra- 
ordinary way,  and  often  not  having  any  effect  at 
all,  usually  protected  guinea-pigs  against  an  in- 
fection of  cholera  bacteria  which  otherwise 
would  have  been  fatal  (protection  was  often  im- 


IMMUNITY.  323 

parted  by  the  use  of  so  small  a  quantity  as 
o.oicc.).  This  protection  was  positive  against 
intraperitoneal  infection,  less  sure  against  in- 
fection by  the  stomach,  and  not  effective  at  all 
against  the  cholera  toxin.  R.  Pfeiffer  now  tests 
for  the  presence  of  immunity  by  using  a  culture 
obtained  from  the  last  epidemic  and  which  he 
regards  as  a  typical  cholera  culture.  He  con- 
ceives that  this  method  is  available  for  deter- 
mining whether  cultures  of  comma  bacilli  are 
"  true  "  cholera  bacteria  and  for  distinguishing 
them  sharply  and  without  fail  from  other 
comma  bacilli.  The  method  in  brief  is  this  :  a 
guinea-pig  is  infected  with  the  culture  of  comma 
bacilli  the  nature  of  which  it  is  desired  to  deter- 
mine ;  if  the  anti-substances  produced  in  the 
serum  of  this  animal  are  able  to  protect  against 
inoculation  with  the  test  culture,  then  the  cul- 
ture in  question  is  true  cholera ;  if  it  is  not 
capable  of  protecting  against  infection  with  the 
test  culture,  the  germs  are  considered  not  to  be 
cholera  bacteria.  This  test  or  standard  is  how- 
ever quite  indefensible,  since  it  takes  for  grant- 
ed the  very  thing  to  be  proved.  I  obtained  in 
Hamburg  several  cultures  from  severe  cholera 
cases  that  occurred  in  this  very  epidemic  of 
1892,  and  which  culturally  were  absolutely 
alike  ;  yet  the  serum  obtained  through  inocu- 
lation failed  to  produce  reciprocal  immunity. 


324  BACTERIOLOGY. 

At  the  time  of  this  epidemic  a  culture  of  a 
comma  bacillus  was  obtained  from  the  Nord- 
hafen  in  Berlin  which  agreed  in  all  respects 
with  Koch's  comma  bacteria,  and  on  this  basis 
the  river  Spree  was  orEcially  declared  to  be 
"  infected  "  ;  afterwards  this  species  was  found 
not  to  respond  to  Pfeiffer's  reaction,  and  so 
could  no  longer  be  regarded  as  a  cholera  germ. 
Inoculation  with  the  Finthen  cholera  germ 
did  not  yield  me  a  serum  that  would  protect 
against  the  cholera  bacteria  of  Hamburg.  R. 
Pfeiffer  himself  did  not  obtain  from  the  Mas- 
sowah  cholera  germ  a  serum  that  would  protect 
against  his  test  culture,  although  this  Mas- 
sowah  culture  was  obtained  in  the  course  of 
a  severe  cholera  epidemic  of  Indian  origin 
which  had  furnished  us  with  one  of  our  most 
virulent  cholera  cultures  ;  and  a  culture  of  this 
same  germ  had  caused  a  severe  case  of  labora- 
tory cholera  in  Italy !  Rumpel  in  1893  ob- 
tained two  cultures  of  comma  bacilli  from 
cholera  cases  that  had  ended  fatally  and 
these  when  non-luminous,  protected  against 
Pfeiffer's  test-culture,  but  if  employed  at  a  time 
when  they  were  phosphorescent  afforded  no  pro- 
tecting serum.  Ruete  and  Enoch  found  finally 
that  inoculation  with  a  culture  of  the  Fink- 
ler-Prior  comma  bacillus  afforded  serum  that 
would  protect  against  Pfeiffer's  test-culture. 


IMMUNITY.  325 

The  principle  of  specificity  as  exemplified  in 
the  setting  up  of  "  true  "  species  of  bacteria 
can  evidently  be  carried  to  such  an  excess  as 
to  lead  eventually  to  scientific  absurdities. 
The  error  made  by  R.  Pfeiffer  is  due  to  the 
fact  that  in  consequence  of  the  post  hoc,  ergo 
propter  hoc  fallacy,  he  conceived  that  immuni- 
zation was  brought  about  by  the  antitoxin. 

Ehrlich  was  the  first  to  attempt  to  measure 
the  efficacy  of  the  toxins.  Such  a  calculation 
appears  somewhat  more  exact  than  it  really  is 
because  the  outcome  of  an  attempt  to  establish 
the  degree  of  toxicity  of  a  substance  depends 
upon  the  animal  subjected  to  experiment,  and 
the  animal,  for  the  reason  that  it  is  a  living 
organism,  often  reacts  more  delicately  than  a 
balance  to  be  sure,  but  never  so  precisely. 
The  process  of  determining  the  strength  of  a 
dose  is  as  follows.  The  minimal  fatal  dose  of 
the  poison  is  first  determined  ;  for  instance 
diphtheria  cultures  may  be  obtained,  o.icc.  of 
which  is  sufficient  to  kill  a  guinea-pig  of  500 
grams  weight  inside  of  24-48  hours,  and  teta- 
nus cultures,  o.ooacc,  of  which  can  kill  a 
guinea-pig,  the  solid  poison  being  estimated  to 
be  more  potent  than  strychnine  or  even  prussic 
acid.  Such  a  degree  of  immunity  as  may  be 
gained  by  an  animal  through  protective  inocu- 
lation enables  it  to  withstand  many  times  the 


326  BACTERIOLOGY. 

minimal  fatal  dose,  and  injection  of  the  minimal 
fatal  dose  itself  is  now  borne  without  reaction. 

Behring  and  Ehrlich  made  the  estimation 
outside  of  the  animal  body  by  mixing  a  definite 
quantity  of  the  toxic  solution  obtained  from 
cultures  with  graduated  quantities  of  the  pro- 
tective serum.  In  this  way  mixtures  of  vary- 
ing grades  of  action  are  obtained,  first  those 
that  manifest  unmistakable  toxic  action,  next 
those  by  which  the  course  of  the  disease  is 
retarded,  then  those  in  which  only  local  pheno- 
mena make  their  appearance,  and  finally  those 
in  which  the  quantity  of  serum  injected  at 
the  same  time  with  the  toxin  completely  in- 
hibits the  action  of  the  latter.  A  serum  o.icc 
of  which  renders  entirely  impotent  ten  times 
the  minimal  lethal  dose  is  termed  normal  serum 
One  cubic  centimeter  of  this  normal  serum  is 
called  an  immunization  unit.  If  o.oicc.  of  a 
serum  confers  protection,  the  serum  would 
possess  ten  immunization  units. 

Roux's  method  of  calculation  starts  with  the 
living  animal.  He  computes  the  body  weight 
of  the  animal  which  is  protected  against  the 
minimal  lethal  dose  by  a  unit  volume  of  serum. 
He  employs  ice.  of  a  toxin  solution,  o.icc.  of 
which  kills  a  guinea-pig  of  500  grams  in  24 
hours  ;  this  starting-point,  therefore,  is  the 
same  as  that  of  Behring  and  Ehrlich.  If  ice. 


IMMUNITY.  327 

of  this  toxin  solution  is  nullified  by  0.0500. 
of  a  serum,  on  simultaneous  injection,  ice.  of 
the  serum  evidently  protects  100,000  grams  of 
animal  against  the  minimal  dose,  and  the  im- 
munizing value  is  hence,  according  to  Roux, 
100,000.  With  very  potent  serum,  infini- 
tesimal quantities  are  sufficient  to  produce 
immunity  ;  in  diphtheria  about  ywVo  F  °f 
the  body  weight  and  in  tetanus  about  one-tril- 
lionth  can  protect  the  animal. 

The  Nature  of  Antitoxin. 

These  facts  must  not  cause  us  to  mistake 
the  action  of  antitoxin  for  a  neutralization,  a 
direct  nullifying  of  the  poison  by  the  antidote 
in  the  sense  of  a  molecular  interchange  siich 
as  occurs  between  acid  and  alkali,  although 
such  a  comparison  has  been  used  by  Behring. 
The  action  of  antitoxin,  so  far  as  at  present 
known,  is  simply  that  of  a  cell  stimulus.  We 
are  even  able  to  prove  directly  that  the  protec- 
tive serum,  or  the  supposititious  antidote  in  it, 
does  not  actually  destroy  or  neutralize  the 
poison  used  in  immunizing  or  in  establishing 
a  tolerance  of  poison,  but  that  both  bodies  can 
exist  side  by  side. 

Buchner  prepared  a  mixture  of  tetanus  toxin 
and  serum  which  was  neutral  in  the  Behring- 


328  BACTERIOLOGY. 

Ehrlich  sense,  and,  upon  injection  of  the  mix- 
ture into  white  mice  no  influence  of  the  toxin 
was  to  be  noted.  Had  it  been  a  real  neutrali- 
zation we  should  expect  that  a  correspondingly 
large  quantity  of  this  mixture  would  have  had 
no  effect  upon  other  animals.  When  the  mix- 
ture was  inoculated  into  guinea-pigs,  however, 
signs  of  tetanus  poisoning  made  their  appear- 
ance. In  reality,  therefore,  toxin  and  antitoxin 
could  not  have  acted  directly  one  upon  another, 
but  both  substances  must  have  exerted  their 
effect  in  the  animal  organism  side  by  side.  A 
partial  nullification  and  prevention  of  the  toxic 
action  does  appear,  to  be  sure,  in  such  cases,  but 
I  was  able  to  bring  about  the  same  result  by 
mixing  enzymes  with  the  toxin.  A  mixture 
of  canine  serum  and  rabbit  serum  acts  less 
powerfully  upon  the  typhoid  bacteria  than  does 
either  serum  by  itself  (Buchner).  One  kind 
of  active  proteid  body,  therefore,  seems  to  act 
to  some  extent  upon  another,  but  this  action 
is  not  always  sufficient  to  destroy  the  toxic 
power  of  a  mixture,  and  on  the  other  hand  an 
antagonistic  action  of  this  sort  is  not  usually 
specific,  but  is  wholly  general  in  character  ;  for, 
according  to  Behring,  it  is  possible  to  dimin- 
ish the  toxic  power  of  the  culture  fluids  with 
use  of  iodine  terchloride,  and  even,  according 
to  Vaillard,  with  simple  iodine. 


IMMUNITY.  329 

Roux  and  Vaillard  found  that  a  mixture  of 
tetanus  toxin  and  tetanus  antitoxin  which  was 
wholly  without  effect  upon  healthy  animals, 
caused  tetanus  in  animals  of  the  same  species 
which  had  previously  suffered  from  other  dis- 
eases and  thereby  become  weakened.  They 
discovered  also  that  healthy  animals  which  had 
supported  inoculation  with  the  mixture  appar- 
ently without  any  effect,  subsequently  devel- 
oped tetanus  when  inoculated  later  with  the  pro- 
ducts of  other  bacteria;  at  least  part  of  the  toxin 
had  remained  in  the  body  of  the  animal  for 
several  days  without  producing  any  effect,  but 
also  without  being  destroyed. 

Calmette,  Phisalix  and  Bertrand  found  that 
snake-venom,  abrin  and  ricin  are  destroyed  by 
heat  less  easily  than  are  the  respective  anti- 
dotes found  in  the  serum  after  the  establish- 
ment of  a  tolerance  of  these  poisons.  If  a 
mixture  of  one  of  these  toxins  and  its  antidote 
be  heated,  the  antidote  is  the  first  to  be  de- 
stroyed, the  poison  remaining  behind.  By 
heating  such  mixtures  to  68°-7o°  these  ob- 
servers demonstrated  that  the  poisons  persist 
in  spite  of  the  treatment,  and  therefore  can  not 
have  been  neutralized  or  destroyed  by  the  anti- 
dotes. On  the  other  hand,  when  a  mixture  of 
the  diphtheria  toxin  and  its  antidotal  serum  is 
heated  to  68°  the  toxin  is  destroyed  first  and 


330  BACTERIOLOGY. 

the  strength  of  the  antidotal  element  is  merely 
weakened. 

We  may  now  ask  what  are  these  "  specific  " 
anti-substances  found  in  the  blood  after  the 
establishment  of  a  "  specific  "  habituation  to 
certain  poisons  ?  They  are,  so  far  as  we  can 
judge,  different  from  the  real  bacterial  poisons, 
from  the  alexins  or  defensive  proteids  of  the 
blood  and  from  the  ferments,  since  in  contrast 
to  the  toxins  they  are  able  in  general  to  with- 
stand higher  temperatures,  and  greater  ex- 
posure to  insolation  and  putrefaction  without 
becoming  impotent.  Even  if  they  possess  the 
same  degree  of  resistance  or  are  less  resistant 
(as  is  anti-abrin  compared  with  abrin),  they 
differ  in  other  respects.  So  long  as  the 
"  specific"  protective  inoculations  are  alone 
considered,  the  participation  of  the  bacteria 
must  be  regarded  as  the  sole  or  essential  de- 
termining factor  in  the  production  of  these 
substances. 

Two  interesting  observations  upon  man  also 
favor  the  view  that  bacteria  take  part  in  the 
formation  of  the  anti-substances.  Buschke, 
after  he  had  infected  himself  with  material  sus- 
pected of  harboring  tetanus  virus,  used  a 
prophylactic  injection  of  tetanus  serum  and 
observed  that  tetanus-like  symptoms  ensued. 
Bearing  in  mind  the  great  susceptibility  of  man 


IMMUNITY.  331 

to  tetanus  it  would  seem  from  this  as  if  some 
component  derived  from  the  tetanus  bacteria 
were  present  along  with  the  anti-substances. 
Similarly  Marcuse  observed  in  a  child  after 
the  injection  of  diphtheria  serum  the  appear- 
ance of  paralysis  of  just  such  a  character  as 
would  be  produced  by  diphtheria  toxin. 

But  on  the  other  hand  an  important  fact 
lends  countenance  to  the  view  that  the  cells  of 
the  human  or  animal  organism  which  forms  the 
anti-substance  are  the  more  important  factors. 
If  we  administer  a  given  quantity  of  toxin  in 
the  form  of  many  small  doses  one  after  another, 
and  in  another  instance  inject  the  same  quan- 
tity all  at  once  in  one  large  dose,  the  amount 
of  antitoxin  found  in  the  animal  after  the  same 
lapse  of  time  is  considerably  larger  in  the 
first  case  than  in  the  second.  (Roux.)  The 
numerous  small  stimuli  are  in  this  case  able 
to  act  cumulatively  upon  the  body-cells  con- 
cerned in  the  formation  of  the  antagonistic 
substances,  while  by  the  other  method  a  great 
part  of  the  single  large  dose  of  foreign  active 
proteid  is  at  once  eliminated.  If  it  were  a  case 
of  simple  chemical  combination,  the  total 
quantity  of  antitoxin  formed  would  neces- 
sarily be  the  same  in  both  cases  in  the  same 
period  of  time.  The  toxins  therefore  act  as 
stimuli  upon  the  body-cells,  and  these  forth- 


332  BACTERIOLOGY. 

with  contribute  to  the  blood  new  defensive  sub- 
stances. 

The  "  specificity  "  of  protective  inoculation 
with  the  anti-substances  depends  therefore  only 
apparently, — just  as  in  the  case  of  protective 
inoculation  with  living  parasites  and  with 
metabolic  products, — upon  the  "  specificity  " 
of  the  microbes. 

It  would  seem,  accordingly,  that  the  "  speci- 
fic anti-substances  "  of  the  blood  resulting  from 
"  specific  "  immunization  and  establishment  of 
tolerance  of  poisons  are  substances  derived 
from  "  specific  "  disease  germs,  worked  over, 
however,  in  a  peculiar  way  and  made  active  by 
u  specific  "  body  cells,  or  brought  into  union 
with  an  active  proteid  of  the  body  to  form  a 
new  and  active  substance.  Emmerich  has 
suggested  the  name  "  immunizing  proteids  " 
for  these  hypothetical  substances. 

Do  the  Antitoxins  Bring  About  Specific 
Immunity  ? 

The  fact  that  new  bodies  of  this  sort  are 
formed,  that  is  to  say  that  new  qualities  ap- 
pear in  the  organism,  does  not  necessarily 
prove  that  these  substances  are  the  ones  that 
exert  the  specific  protective  effect.  I  have  al- 
ready urged  this  point,  but  have  been  unable 


IMMUNITY.  333 

to  carry  conviction  until  recently,  supported 
by  Gottstein  and  Schleich,  I  proved  that  a 
specificity  of  this  kind  must  depend  chiefly 
upon  the  fact  that  when  a  man  acquires  protec- 
tive inoculation  there  must  be  stimulation  or 
excitation  of  those  particular,  specific  organs, 
tissues,  cell-territories  or  cells  which  are  es- 
pecially involved  in  the  disease  in  question. 
Just  as  bacteria  can  be  separated  into  species, 
so  also  do  differences  exist  between  the  cells 
of  the  different  species  of  host  animals  and  also 
between  the  cells  of  the  various  organs  and 
tissues  of  the  individual  organism ;  the  liver- 
cell  is  not  only  a  cell :  it  is  more  than  that,  it 
is  a  liver-cell,  and  the  liver-cell  of  a  dog  is  not 
only  a  liver-cell,  it  is  the  particular  sort  of 
liver-cell  pertaining  to  a  dog.  What  is  fair  to 
the  bacterium  is  only  fair  to  the  body-cell. 

Still  other  reasons  induce  us  to  declare  for 
the  preponderating  significance  of  the  body- 
cells  and  against  the  determining  influence  of 
the  bacteria  in  bringing  about  the  establish- 
ment of  specific  tolerance  of  poisons.  In  the 
first  place  it  is  very  improbable  that  where  a 
genuine  habituation  to  poison  exists,  or  where 
an  establishment  of  tolerance  of  simple  poisons 
like  ricin  or  abrin  is  effected,  the  habituation  to 
these  poisons  is  bound  up  with  the  formation 
of  an  altogether  new  and  peculiar  foreign  body 


334  BACTERIOLOGY. 

in  the  blood.  Such  an  idea  is  hardly  anything 
more  than  a  hasty  conclusion  ad  hoc.  In  hab- 
ituation  to  alcohol  no  "  anti-alcoholin  "  is 
formed,  in  habituation  to  morphine  no  "  anti- 
morphine,"  and  yet  a  tolerance  of  these  poisons 
is  established  apparently  by  simple  interven- 
tion of  the  body-cells.  The  susceptibility  of 
the  body  to  such  poisons  and  the  degree  of  pro- 
tective action  established,  vary  according  to  the 
method  of  introducing  the  poisons,  the  period  of 
life  and  other  influences.  The  degree  of  habitu- 
ation to  poison  that  may  be  acquired  is  also 
very  different  according  to  the  organs  involved. 
Schleich  has  accustomed  animals  to  receive  with 
impunity  large  doses  of  chloroform,  morphine 
and  cocaine,  and  yet  the  animals  are  never- 
theless poisoned  with  slight  dose's,  when  these 
are  introduced  directly  into  the  brain,  just 
as  in  Pasteur's  method  of  inoculation  in  rabies. 
The  highest  grades  of  poison  tolerance  show 
indeed  a  definite  dependence  upon  the  method 
by  which  the  tolerance  has  been  brought  about. 
This  can  signify,  however,  nothing  less  than 
a  direct  dependence  of  these  conditions  of  tol- 
erance or  immunity  upon  the  cellular  influ- 
ences of  the  human  body,  and  these  influences 
can  certainly  be  brought  to  bear  in  the  absence 
of  any  specific  anti-substances  in  the  blood. 
The  poison  tolerances  belong  in  the  same  cate- 


IMMUNITY.  335 

gory  with  the  phenomena  which  have  been 
associated  with  the  name  of  Mithridates,  the 
king  of  Pontus,  who  fortified  himself  against 
poison  by  taking  antidotes.  The  peculiar, 
specific  influence  of  the  body-cells  may  in  itself 
suffice  for  our  complete  understanding  of  the 
matter.  A  specific  influence  of  this  kind,  how- 
ever, as  may  be  inferred  from  our  previous  ex- 
position, is  dependent  upon  specific  external 
conditions  only  in  so  far  as  the  surroundings 
stimulate  or  set  free  predispositions  already 
existing,  as  when  for  instance  they  cause  a 
specially  marked  activity  of  the  body  cells 
which  differs  from  the  former  condition  only 
in  a  quantitative  direction.  Since  the  body- 
cells  are  not  directly  available  for  experiment, 
and  we  are  often  able  to  gain  information  as  to 
their  content  of  energy  only  indirectly  through 
the  setting  free  of  energy,  many  investigators 
draw  the  fallacious  conclusion  that  the  speci- 
ficity of  the  exciting  germ  is  the  sole  determin- 
ing factor  and  that  a  new  quality  is  involved 
in  the  change  that  takes  place  in  the  organism. 
The  fact  is  important  also  that  the  active 
anti-toxins  generally  confer  no  immunity.  If 
cultures  of  tetanus  or  diphtheria  bacteria  or  of 
some  other  parasite  be  heated  to  about  65°-7o° 
their  specific  toxic  activity  is  taken  away,  while 
their  capacity  for  conferring  immunity  upon 


336  BACTERIOLOGY. 

animals  still  continues  in  force.  Such  heated 
cultures  have  gained  at  the  same  time  in  place 
of  their  toxic  action,  a  protective  power  similar 
to  that  shown  by  the  serum  of  animals  made 
"  specifically  "  tolerant  of  poison.  In  my  lab- 
oratory Bunzl-Federn  treated  culture  fluids 
with  digestive  ferments,  and  succeeded  in  the 
case  of  pneumonia  in  obtaining  protective  sub- 
stances of  the  kind  that,  according  to  Behring, 
are  supposed  to  exist  only  in  the  form  of  the 
anti-substances  of  the  blood-serum,  in  those 
organisms  that  are  tolerant  of  poison.  Klem- 
perer  and  Kriiger,  and  Nencki  and  Smirnow 
reached  the  same  result  by  making  use  of  the 
action  of  the  electric  current  upon  toxic  bac- 
terial cultures.  The  hypothesis  is  untenable 
that  in  the  latter  experiments,  which  were  con- 
ducted outside  of  the  body,  antagonistic  sub- 
stances are  produced  from  the  poisons.  As 
with  other  bodies  of  this  kind  the  poisons  are 
destroyed  by  the  treatment ;  the  bacterial  cell 
substances  which  confer  immunity  simply 
become  modified,  since  the  cultures  thus  de- 
prived of  poison  are  capable  of  bestowing  im- 
munity. 

The  same  result  follows  from  other  experi- 
ments. The  anti-substances  vanish  from  out 
of  the  blood  v/ith  relative  quickness,  and  hence 
protective  inoculation  with  these  substances 


IMMUNITY.  337 

has  been  considered  by  Beliring  and  Ehrlich 
as  "  passive."  Now  in  the  passive  immuniza- 
tion that  is  effected  in  the  case  of  diphtheria, 
the  animal  still  remains  immnne  after  the  anti- 
substances  have  disappeared  from  the  blood, 
and  experiments  made  outside  of  the  body  show 
that  the  blood  has  been  robbed  of  all  protective 
power.  The  explanation  of  this  is  to  be  found 
in  the  fact  that  the  poison  tolerance  was  effected 
by  means  of  old  cultures  which  contained, 
besides  the  poison,  those  bacterial  cell  sub- 
stances which  have  already  been  shown  to  be 
the  most  important  factors  in  active  immuni- 
zation (p.  311). 

If  rabbits  are  inoculated  with  toxin-free  te- 
tanus spores  together  with  lactic  acid,  the  ani- 
mals become  immune,  but  their  serum  imparts 
to  other  animals  no  protection  against  tetanus 
(Roux  and  Vaillard).  Immunity  and  poison 
tolerance  are  evidently,  in  this  instance,  not 
associated  with  the  presence  of  antitoxin  in 
the  blood.  Behring  has  found  that  it  is  pos- 
sible by  means  of  too  frequent  or  too  large  in- 
jections of  poison  to  immunize  animals  so 
highly — or  more  correctly  to  administer  to 
them  so  much  poison — that  they  exhibit  symp- 
toms of  poisoning  and  become  hyper-sensitive 
to  the  toxin,  in  spite  of  the  fact  that  their  serum 
displays  the  most  powerful  antitoxic  action. 


22 


338  BACTERIOLOGY. 

In  such  a  case  the  power  of  forming  antitoxin 
is  present  without  a  corresponding  immunity. 
According  to  Mosso,  the  blood  of  the  eel 
possesses  poisonous  qualities,  and  according  to 
Calmette,  the  blood  of  both  poisonous  and  non- 
poisonous  serpents,  of  salamanders  and  of  toads 
is  also  poisonous  ;  the  toxicity  of  the  blood  of 
all  snakes  is  approximately  the  same,  whereas 
snake-venom  shows  the  greatest  differences  in 
the  different  species.  In  contrast  to  snake- 
venom,  which,  according  to  Fayrer  and  Ward, 
can  withstand  a  temperature  as  high  as  75° 
and  is  weakened  only  at  8o°-9O°,  the  poison 
of  the  snake-blood,  like  the  generality  of  the 
active  bodies  found  in  the  blood,  is  destroyed 
at  65°-7o°.  These  facts  demonstrate  the  in- 
dependence of  the  two  poisons, 'one  of  another, 
and  this  independence  is  substantiated  by  vari- 
ous experiments.  According  to  Sewall,  whose 
experiments  have  been  extended  by  Calmette, 
Phisalix  and  Bertrand,  animals  can  be  made 
immune  against  snake-venom,  and  also  against 
poisonous  snake  blood  (Calmette).  Toxic 
serpent  blood  kills  animals  which  are  immune 
against  serpent-venom,  and  conversely.  In 
spite  of  this  difference  of  action,  one  active 
poison  does  influence  the  other.  Serpent  blood 
that  is  normally  poisonous  may  become  tem- 
porarily non-poisonous  in  consequence  of  the 


IMMUNITY.  339 

establishment  of  a  tolerance  of  the  organism 
to  serpent  venom. 

The  blood  of  the  hedgehog,  according  to 
Phisalix  and  Bertrand,  is  poisonous  to  guinea- 
pigs.  If  this  blood  be  heated  and  its  poison- 
ous qualities  destroyed,  it  is  able  to  protect 
guinea-pigs  against  the  bite  of  the  common 
adder.  The  protection  against  the  poison  in 
this  case  evidently  does  not  depend  upon  the 
action  of  an  anti-substance,  nor  can  it  be  due 
to  the  neutralization  of  the  poison  by  a  specific 
antidote. 

When  immunization  is  accompanied  by  the 
acquisition  of  a  tolerance  of  poison  it  is  fre- 
quently the  case  that  no  antidote  for  the 
specific  poison  can  be  discovered  in  the  serum 
of  the  protected  animal.  Emmerich  first 
proved  for  swine-erysipelas  and  pneumonia 
that  the  active  bodies  to  which  the  properties 
of  the  protective  serum  are  due  act  not  anti- 
toxically,  but  bactericidally  ;  that  is,  that  they 
kill  the  specific  bacteria.  Novy  established 
the  same  thing  for  the  swine-plague,  and  R. 
Pfeiffer  has  recently  discovered  that  the  same 
fact  is  true  of  cholera. 

In  the  latter  case  the  normal  serum  of 
healthy  animals  may  act  bactericidally,  al- 
though in  a  lesser  degree  than  that  of  animals 
specifically  inoculated.  On  this  ground  it 


34O  BACTERIOLOGY. 

may  be  questioned,  as  in  the  case  of  the  anti- 
toxin, whether  the  bactericidal  substances  of 
the  serum  are  compounds  of  the  bacterial  cell 
substances  with  the  active  body  proteids,  or 
whether  they  are  simply  body  proteids.  On 
the  first  supposition,  it  might  be  expected  that 
any  newly-formed  compound  would,  because  of 
its  recent  origin,  be  especially  reactive  and 
able  to  act  as  an  intense  stimulus  to  the  body 
cells.  The  appearance  in  this  case  of  peculiar 
bactericidal  and  antitoxic  substances  would 
be  only  apparently  traceable  to  the  emergence 
of  new  qualities,  to  the  creation  of  "  specific  " 
substances.  The  hypothesis  might  rather  be 
held  that,  through  the  action  of  a  chemical 
stimulus  especially  appropriate  on  account  of 
its  greater  reactivity,  what  happens  is  merely 
that  a  larger  quantity  of  the  same  bactericidal 
or  antitoxic  substance  already  present  makes 
its  appearance  in  the  blood  of  immunized  ani- 
mals, and  that  a  normal  animal  in  a  healthy 
condition  already  possesses  the  substance  as  a 
means  of  defense,  but  in  a  smaller  amount. 
In  spite  of  the  proof  that  elements  of  "  spe- 
cific "  microbes  are  concerned  in  the  produc- 
tion of  the  antitoxins  or  germicidal  substances 
found  in  the  blood  of  animals  "  specifically  " 
immunized  or  made  tolerant  of  poison,  it  is 
very  probable  that  these  "  specific  "  bacterial 


IMMUNITY.  341 

substances  merely  furnish,  the  necessary  stim- 
ulus. The  peculiar  antitoxic  and  bactericidal 
action  observed  in  such  cases  is  due  to  the 
qualities  of  the  substances  which  are  formed  in 
the  serum  in  larger  quantities  in  those  animals 
made  immune  or  tolerant  of  poison  ;  normal 
animals  already  contain  the  same  "  specific  " 
substances  but  in  smaller  quantities.'  The 
property  of  specificity  which  is  seemingly  a 
newly-acquired  quality,  may  not  unreasonably 
be  conceived  of  as  a  quantitative  variation  and 
as  dependent  upon  the  bringing  into  action  of 
normal  forces  by  appropriate  stimuli. 

The  formation  of  antitoxin  is  certainly  noth- 
ing but  an  accessory  or  concomitant  to  arti- 
ficial immunity  and  habituation  to  poison,  and, 
since  it  is  not  necessary  for  the  acquisition  of 
these  properties,  it  is  not  their  cause. 

Before  we  discuss  the  consequences  of  this 
fact  let  us  consider  another  side  of  protective 
inoculation  in  general. 

Anticipatory    Inoculations — Specific    Curative 
Inoculations — Specific  Serum  Therapy. 

In  considering  Brehmer's  method  for  the 
cure  of  tuberculosis,  I  have  already  mentioned 
that  the  same  remedies  which  nature  employs 
to  convert  a  predisposition  toward  disease  into 


342  BACTERIOLOGY. 

immunity  and  thereby  prevent  disease,  may 
also  be  used  to  cure  the  disease.  The  same 
thing  holds  good  of  protective  inoculations, 
which  were  at  first  used  to  prevent  the  break- 
ing out  of  disease,  or  to  render  an  attack  of 
disease  more  mild.  When  disease  broke  out 
before  the  protective  inoculation  had  been 
made,  the  so-called  anticipatory  inoculation 
was  sometimes  resorted  to.  Inoculation  was 
performed  in  the  usual  way  in  the  hope  that 
an  immune  condition  would  develop  quickly 
enough  to  protect  the  still  uninjured  individ- 
ual. This  was  practiced,  for  example,  in 
human  small-pox  with  vaccine,  and  still  more 
frequently  in  sheep-pox  with  ovine. 

Pasteur  introduced  an  entirely  new  idea. 
Immunity  frequently  makes  its  appearance 
very  quickly.  This  was  regarded  erroneously 
as  the  manifestation  of  a  specific  character,  but 
so  far  as  it  has  been  controlled  by  subsequent 
investigations,  it  seems  often  to  be  due  merely 
to  the  sudden  rousing  to  activity  of  the  normal 
protective  forces  of  the  body  by  the  stimulus 
of  the  invasion.  On  the  other  hand,  the  infec- 
tion, starting  from  the  moment  of  penetration 
of  the  disease  germs,  requires  time  to  become 
manifest  as  a  due  sequence  to  the  multiplica- 
tion of  the  parasites  and  their  formation  of 
poison  ;  this  interval  is  called  the  period  of  in- 


IMMUNITY.  343 

cubation.  If  the  period  of  incubation  be  long 
the  disease  may  require  days  before  showing 
itself  openly ;  perhaps  in  this  intermediate 
period  it  may  be  possible  to  bring  about  a  suc- 
cessful protective  inoculation,  even  although  a 
successful  infection  had  previously  occurred. 
Such  was  Pasteur's  train  of  thought,  and  he 
sought  to  accomplish  the  desired  end  by 
making  use  of  the  much-discussed  method  of 
inoculation  against  rabies.  If  we  do  not  neg- 
lect the  local  factor  in  protective  inoculation — 
already  several  times  mentioned — and  the  way 
in  which  immunity  spreads  from  the  place  of 
infection  to  the  blood  and  central  nervous  sys- 
tem, it  must  be  unconditionally  admitted  that 
Pasteur's  method  of  treating  rabies  has  cer- 
tainly achieved  success  in  cases  in  which  no 
favorable  issue  could  have  been  hoped  for  from 
the  use  of  other  means.  Partial  success  has 
been  attained  also  in  the  method,  described 
on  p.  305,  of  inoculation  with  the  metabolic 
products  of  bacteria,  carried  out  on  the  same 
theory.  That  is  to  say,  the  incorporation  of 
the  protective  substances  is  resorted  to  only 
after  the  disease  has  broken  out. 

In  the  same  group  of  conceptions  belongs 
the  use  of  proteids  for  curative  purposes.  The 
first  experiments  were  made  in  1884-86,  by 
Ferran  and  Zaeslein,  who  administered  dead 


344  BACTERIOLOGY. 

cultures  of  comma  bacilli  to  cholera  patients. 
Koch's  experiments  with  tuberculin,  in  1890, 
are  the  best  known  experiments  of  this  class, 
but  the  results  obtained  have  not  approxi- 
mately fulfilled  the  hopes  aroused.  Such 
favorable  results  with  this  substance  as  have 
been  recorded  may  be  attributed  to  the  power 
of  tuberculin  to  excite  inflammation,  (p.  313), 
a  point  wholly  missed  by  Koch  and  discovered 
by  Hueppe  and  Scholl.  F.  and  G.  Klemperer 
have  used  the  proteids  of  Diplococcus  lanceo- 
latus  to  combat  pneumonia,  and  E.  Frankel 
those  of  the  typhoid  bacteria,  as  protection 
against  typhoid  fever,  but  without  specially 
successful  results. 

In  those  cases  which  are  to  be  regarded  as 
instances  of  rapid  immunization  it  is  necessary 
to  meet  any  increase  in  the  intensity  and  dura- 
tion of  the  disease,  by  administering  stronger 
or  more  potent  doses  of  the  immunizing  sub- 
stance, so  that  the  danger  of  poisoning  the 
organism  is  increased.  Acting  upon  his  con- 
ception of  passive  immunity,  Behring  thought 
it  possible  to  avoid  completely  this  danger, 
and  to  cure  certainly  and  without  risk  of  harm, 
by  introducing  the  protective  serum,  even  after 
successful  infection  had  been  brought  about. 
This  is  the  real  significance  of  the  serum  ther- 
apy, although,  from  the  beginning,  it  has  been 


IMMUNITY.  345 

represented  by  Behring  in  the  light  of  an  en- 
tirely ontological  specificity  of  the  micro-para- 
sites. The  serum  therapy  must  be  placed, 
therefore,  in  the  same  category  with  Pasteur's 
inoculations  for  rabies,  and  not  in  that  with 
Koch's  inoculations  with  tuberculin.  Accord- 
ing to  this  view  one  "  species  "  of  animal,  man 
for  example,  is  naturally  immune  against  a 
"  species  "  of  micro-parasite  ;  immunity  against 
the  "  specific  "  disease  of  small-pox  can  be 
gained  only  through  "  specific  v  small-pox 
virus,  "  specific  "  tolerance  of  the  toxin  of 
diphtheria,  only  through  the  "  specific  "  diph- 
theria toxin  ;  hence  a  complete^  immune 
body  must  contain  "  specific  "  antidotes  against 
all  these  disease  germs  and  also  against  their 
poisons. 

The  logical  consequence  of  this  doctrine  as 
Pasteur,  Koch  and  Behring  have  shown,  is 
that  against  every  "  specific  "  infectious  dis- 
ease, a  "  specific  "  protective  inoculation  or  an 
attempt  to  establish  a  u  specific  "  poison  toler- 
ance must  be  adopted  as  the  method  of  preven- 
tion or  cure.  The  methods  which  have  been 
employed  for  this  purpose  have  been  differently 
conceived  and  carried  out  in  different  epochs. 
In  1638,  a  method  of  this  sort  was  followed  by 
Robert  Fludd,  who  prepared  a  remedy  against 
consumption  from  the  sputum  of  consump- 


BACTERIOLOGY. 

tives.  This  doctrine  was  set  forth  still  more 
lucidly  in  1833,  upon  the  basis  of  the  funda- 
mental proposition  laid  down  by  the  German 
veterinarian  Lux,  that  all  contagious  diseases 
carry  in  their  own  contagious  matter,  the 
remedy  for  their  own  cure.  Formerly,  this 
principle  was  called  Isopathy,  now  it  is  called 
"  Specific  Therapy,"  in  order  that  we  may 
avoid  the  appearance  of  having  learned  any- 
thing from  our  predecessors,  or  of  causing  it 
to  seem  as  if  scientific  medicine  had  any  rela- 
tions whatever  with  such  scorned  doctrines  as 
Isopathy  or  Homeopathy.  In  reality,  it  is  the 
same  dogma  in  another  garb.  Lux,  for  ex- 
ample, prepared  hydrophobin  against  rabies, 
variolin  against  small-pox,  pneumophthisin 
against  consumption — Koch  now  calls  it  tu- 
berculin and  Klebs  anti-phthisin — and  scar- 
latin  against  scarlet  fever.  But  the  chief  dif- 
ference in  the  preparations  of  Lux,  was  that 
the  first  was  prepared  for  the  dog,  the  others 
for  the  cat. 

The  fact  has  already  been  mentioned  (p.  317) 
that, — before  Behring  and  Kitasato, — Ferran, 
Hericourt  and  Richet,  and  Babes  and  Lepp 
sought  and  with  partial  success,  to  cure  infec- 
tions already  in  progress  by  the  use  of  protect- 
ive serum.  Waggish  philologists  maintain,  to 
be  sure,  that  the  practice  is  even  much  older, 


IMMUNITY.  347 

and  that  Horace,  in  his  words  "  sero  medicina 
paratur  "  must  have  been  expressing  his  con- 
viction that  the  universal  cure  would  be  pre- 
pared from  serum.  The  principal  service  in 
the  development  of  serum  therapy  was  rend- 
ered, however,  by  Behring,  who  also  knew  how 
to  interest  in  the  problem  careful  fellow-work- 
ers like  Kitasato,  Ehrlich,  Wernicke  and  others, 
with  the  result  that  in  the  minds  of  many 
workers  the  different  varieties  of  curative  se- 
rum now  seem  to  present  the  sole  opportunity 
for  medical  investigation,  as  some  years  ago, 
under  the  influence  of  the  tuberculin  investi- 
gation, was  the  case  with  the  proteids. 

The  starting  point  of  the  serum  therapy  is 
the  observation  that  animals,  after  being  suc- 
cessfully infected  regain  their  health  when 
treated  with  a  subcutaneous  injection  of  the 
serum  of  immunized  animals.  The  result 
varies  according  to  the  time  which  has  elapsed 
since  the  infection.  If,  for  example,  the  muc- 
ous membrane  of  the  trachea  is  infected  with 
diphtheria  bacilli,  the  injection  of  serum  un- 
der the  skin  causes,  within  24-26  hours,  the 
fibrinous  exudate  of  the  mucous  membrane  to 
be  thrown  off,  stops  the  poisonous  action,  and 
prevents  further  general  infection.  When  the 
infection  is  subcutaneous  the  fibrinous  exu- 
date in  the  derma  is  changed  by  the  use  of 


348  BACTERIOLOGY. 

the  serum  into  a  suppurative  one,  so  that,  by 
sloughing  off  of  the  necrotic  tissue  local  heal- 
ing makes  its  appearance,  and  this  is  accom- 
panied by  the  prevention  of  general  infection 
and  poisoning.  If  the  serum  injection  be  de- 
layed more  than  36  hours,  the  local  disturb- 
ance may  still  frequently  be  healed,  but,  on  the 
other  hand,  general  infection  is  not  prevented 
and  is  only  retarded  in  its  course. 

Clinging  to  his  notion  of  a  "  passive  "  pro- 
tective inoculation  in  which  only  the  animal 
producing  the  serum  incurs  risk,  while  the 
animal  receiving  the  serum  reaps  the  benefit, 
Behring  has  maintained  with  the  greatest 
positiveness  the  absolutely  innocuous  character 
of  the  curative  serum.  But  the  statements 
made  above  on  p.  327  concerning  the  nature 
of  the  anti-substances  of  the  serum  militate 
against  his  view.  If  we  accept  Behring's 
assumption  of  the  purely  specific  nature  of 
the  anti-substances,  the  fact  that  one  com- 
ponent of  these  substances  is  the  bacterial 
toxin  itself,  as  the  cases  of  Buschke  and  Mar- 
cuse  directly  prove,  is  at  variance  with  his 
idea  that  the  anti-sera  are  altogether  harmless. 
The  following  facts  also  are  opposed  to  such  a 
belief. 

Favorable  specific  effects  such  as  an  im- 
munity against  living  parasites  and  an  habitua- 


IMMUNITY.  349 

tion  to  their  poisons,  are  often  deceptive,  if  we 
fail  to  consider  sufficiently  the  method  of  in- 
troduction or  inoculation.  A  state  of  protection 
against  infection  by  way  of  the  skin  may  be 
present  in  cases  where  immunity  does  not  exist 
at  all  to  infection  by  way  of  the  blood  or  brain  ; 
it  may  be  present  for  one  side  of  the  body  or  for 
one  extremity  and  be  lacking  in  other  regions. 
If  this  fact  is  forgotten  then  it  may  appear  as 
if  the  influence  of  the  body-fluids  were  pre- 
eminent, when  in  reality  the  last  word  rests 
with  the  body-cells.  On  this  basis  Schleich 
has  very  happily  attempted  to  explain  why 
diseases  like  diphtheria,  that  start  from  the 
mucous  membrane  of  the  throat,  or  that  start 
from  the  lungs,  like  pneumonia  and  influenza, 
or  from  the  intestines,  like  cholera,  confer 
upon  the  organism  little  or  no  immunity  from 
another  attack ;  it  is  because  large  tracts  of 
cells  remain  exempt  from  the  effects  of  the 
first  invasion  and  therefore  acquire  no  protec- 
tion. It  seems  as  if  perhaps  toxic  properties 
did  not  exist,  when  in  reality  toxic  manifesta- 
tions are  prevented  only  by  chance.  The  al- 
legedly non-poisonous  diphtheria  serum  itself, 
when  introduced  into  the  derma,  shows  a  toxic 
action  which  manifests  itself  in  pains  and  in 
swellings  of  the  joints  and  in  the  form  of  pe- 
culiar and  obstinate  skin  affections  at  times 


350  BACTERIOLOGY. 

like  those  of  scarlet  fever  or  measles,  as  well 
as  in  bleeding,  kidney  inflammation  and  par- 
alysis, and  it  is  very  doubtful  whether  the  list 
of  possible  injuries  is  yet  exhausted,  for  per- 
haps other  mischievous  effects  may  come  to 
light  with  other  methods  of  use.  Occasionally, 
marked  degeneration  of  heart,  kidney  and 
liver  is  witnessed  immediately  after  the  injec- 
tion of  the  diphtheria  serum ;  and  this  fact 
shows  clearly  that  in  the  use  of  this  antitoxin 
a  danger  exists  of  the  same  character  as  that 
displayed  in  Buschke's  experience  with  the  te- 
tanus serum.  If  the  action  of  the  serum  were 
simply  antitoxic,  danger  of  this  kind  ought 
to  be  impossible.  We  have  the  paradox  of  an 
antitoxin  producing  a  toxic  effect.  According 
to  Emmerich,  animals  that  have  been  treated 
with  diphtheria  serum  afterwards  succumb 
more  easily  to  an,  infection  with  Staphylococci 
and  Streptococci,  a  fact  that  points  also  to  a 
poisonous  action  of  the  antitoxin  upon  the  tis- 
sues. In  man  an  acute  outbreak  of  tubercu- 
losis has  been  more  than  once  observed  to  fol- 
low a  serum  injection.  In  view  of  the  assur- 
ance with  which  Behring  brings  forward  his 
serum  as  something  absolutely  without  pre- 
cedent, terming  it,  by  way  of  contrast  to  all 
previously  known  remedies,  an  "  absolutely 
harmless  remedy,"  it  is  important  to  show  that 


IMMUNITY. 

the  curative  serum  acts,  to  say  the  least,  in  the 
same  manner  as  any  foreign,  active,  ferment- 
like  substance  introduced  into  the  blood  and 
is  not  absolutely  innocuous.  There  is  serious 
disappointment  in  store  for  us  if  we  do  not 
succeed  in  ridding  ourselves  at  once  of  the  fal- 
lacy regarding  the  absolute  harmlessness  of 
the  antitoxin.  With  the  best  intentions  in 
the  world  it  is  impossible  to  understand  what 
is  the  aim  of  such  glorifications  as  those  with 
which  this  remedy  has  been  greeted  and  which 
remind  us  of  the  puffs  of  patent  medicine,  for 
the  simple  facts  prove  that  the  claims  made 
are  not  justified.  On  the  other  hand,  it  is  a 
question  that  is  certainly  open  to  discussion 
whether  or  not  the  employment  of  the  serum 
upon  man  may  still  be  recommended  in  the 
face  of  this  real  danger,  for  the  risk  may  be 
considered  as  overbalanced  by  the  benefits  ob- 
tained in  other  respects.  We  may  reasonably 
hope  that  if  the  chief  danger,  the  infection 
with  the  specific  disease  germ  and  consequent 
poisoning  with  its  toxin,  be  avoided  through 
the  agency  of  the  serum,  nature  will  easily 
dispose  of  the  lesser  accessory  dangers. 
Looked  at  in  this  way,  indeed,  danger  from 
the  use  of  the  tetanus  and  diphtheria  sera  does 
not  seem  to  me  to  be  great. 

The  tetanus  serum,  first  used  upon  man  by 


352  BACTERIOLOGY. 

Tizzoni,  has  up  to  the  present  not  yielded  con- 
spicuously successful  results.  A  decisive  suc- 
cess has,  however,  been  claimed  for  the  diph- 
theria serum,  sometimes  in  an  exceedingly 
unscientific  and  vehement  fashion.  Even  sci- 
entific congresses  take  sides  by  a  majority 
vote  upon  the  question,  purely  scientific  as  it 
is,  and  certainly  not  yet  ripe  for  conclusion, 
and  seek  to  suppress  the  opposing  view.  The 
exaggerations  in  the  tuberculin  affair,  for 
which  afterwards  no  one  was  willing  to  stand 
sponsor,  are  still  sufficiently  mortifying  to 
many  clinicians,  who  by  their  manifest  lack  of 
critical  discernment  in  scientific  matters,  were 
placed  in  a  very  unfortunate  position.  Yet 
this  experience  seems,  inside  of  four  years,  to 
be  completely  forgotten.  At  present  a  some- 
what more  rational  examination  of  the  matter 
is  being  made  with  the  aid  of  collective  in- 
vestigations, but  the  statistical  material  leaves 
almost  everything  to  be  desired. 

In  the  first  place  the  statistical  basis  is  of  a 
very  dubious  character.  Conclusive  control 
experiments  under  absolutely  similar  condi- 
tions do  not  exist  at  all.  In  certain  cases  the 
period  of  introduction  of  the  serum  has  coin- 
cided with  the  occurrence  of  a  mild  epidemic. 
The  mortality  from  diphtheria  varied  from 
1875-1891  between  6.2°/0-34.i%,  indifferent 


IMMUNITY.  353 

cities  (Peer) ;  in  Berlin  (Gottstein)  the 
mortality  from  1880-1894  ranged  between 
23.8 °  0-46. 5  °/0.  Moreover,  the  mortality  is  very 
different  in  the  different  months,  and  in  Berlin 
it  varies  enormously  according  to  the  district, 
in  some  parts  of  the  city  sinking  even  to  9  °/0. 
The  occurrence  of  diphtheria  was  formerly  de- 
termined clinically,  and  the  anginas,  the  mild 
cases  of  throat  inflammation,  were  left  out  of 
account.  According  to  Behring,  however,  the 
diphtheria  serum,  because  it  is  obtained  by  the 
aid  of  pure  cultures  of  diphtheria  bacilli  is 
effective  only  against  those  cases  of  throat 
trouble  that  are  provoked  exclusively  by  the 
Klebs-LofHer  bacteria.  By  adopting  this  clas- 
sification the  gravest  cases  of  septic  diphtheria 
are  excluded.  Further,  it  is  asserted  that  the 
cases  ought  to  be  treated  as  early  as  possible. 
At  present  the  proof  of  the  presence  of  diph- 
theria bacilli  is  sufficient  to  lead  to  treatment 
with  the  curative  serum,  in  spite  of  the  fact 
that  many  cases  in  which  the  diphtheria  bacil- 
lus is  found  never  become  diphtheria  clinically, 
while  on  the  other  hand  many  cases  are  re- 
garded as  pseudo-diphtheria  which  clinically 
might  be  called  true  diphtheria.  Under  the 
influence  of  these  three  fundamental  require- 
ments, namely,  that  the  diagnosis  shall  be 
based  solely  upon  the  presence  of  the 
23 


354  BACTERIOLOGY. 

bacillus,  that  every  such  case  shall  be 
taken  under  treatment  as  early  as  possible, 
and  that  pathological  and  clinical  experience 
shall  be  left  out  of  account,  the  statistics  are 
distorted  so  extravagantly  in  favor  of  the 
serum  therapy,  that  available  material  for  com- 
parison is  lacking.  In  spite  of  this  distortion 
the  result  of  serum  therapy  in  the  hospitals  is 
not  so  favorable  as  that  obtained  in  the  aggre- 
gate. Nevertheless  there  seems  to  exist  in 
the  hospitals  a  certain  diminution  of  the  mor- 
tality through  the  use  of  the  curative  serum, 
if  the  earlier  results  are  used  as  a  basis  of  com- 
parison. It  must  be  borne  in  mind  that  peo- 
ple who  in  quiet  and  coolly  critical  times  would 
not  come  to  the  hospitals,  do,  under  the  influ- 
ence of  such  excitement  as  was  stirred  up  by 
Koch's  tuberculin  and  by  Behring's  serum, 
betake  themselves  to  those  places  where  they 
will  be  treated  with  the  universal  panacea. 
Keeping  in  mind  both  the  essential  change  in 
the  diagnostic  conception  of  diphtheria  and  the 
successful  results  obtained  with  the  serum, 
which  are  really  considerable,  we  are  still  able 
to  say  that  serum  therapy,  as  well  as  protective 
inoculation  with  the  serum,  does  not  possess 
the  character  of  a  "  specific  "  treatment.  From 
a  "  specific  "  cure  we  must  expect  altogether 
different  results  from  those  thus  far  obtained, 


IMMUNITY.  355 

and  above  all  the  effect  upon  severe  cases  must 
be  decisive,  a  feature  in  which  up  to  the  pres- 
ent this  therapy  has  failed. 

The  collected  statistics  of  the  investigation 
in  Germany  during  the  period  from  October 
i,  1894,  to  April  i,  1895,  showed  among  4,450 
ca^es  not  treated  with  serum  a  mortality  of  622 
or  i4.7°/0,  among  5,790  cases  treated  with  serum 
a  mortality  of  552  or  9.5  °/0.  Direct  comparison 
under  exactly  similar  conditions  of  a  sufficient 
number  of  cases  can  however  not  be  made.  I 
do  not  deny  that  the  curative  serum  is  perhaps 
able  to  influence  diphtheria  favorably,  and  that 
hence  some  slight  progress  has  been  made.  I 
deny  only  that  we  have  the  right  to  set  forth 
such  trivial  results  as  "  specific,"  and  such  a 
method  of  treatment  as  the  true  and  only  really 
causal  mode  of  therapy.  On  account  of  the 
merely  moderate  success  so  far  attained,  we 
are  at  liberty  to  hope  that  not  only  so  much 
as  is  claimed,  but  perhaps  even  more,  may 
eventually  be  compassed  in  a  more  simple  and 
reasonable  way. 

The  hope  that  immunization  as  well  as  cure 
may  be  effected  with  the  use  of  the  curative 
serum,  must  be  abandoned  as  I  have  previously 
shown  on  p.  341.  The  slight  protection  which 
the  body  seems  to  gain  from  the  serum  injec- 
tion is  not  specific,  and,  in  contrast  to  a  true 


356  BACTERIOLOGY. 

protective  inoculation,  is  of  very  short  duration ; 
in  diphtheria  it  varies  from  8-14  days  to  10 
weeks  at  most.  It  is  not  possible  to  immunize 
effectively  against  diphtheria  with  curative 
serum,  a  fact  which  on  account  of  the  con- 
fidence we  are  justified  in  attaching  to  really 
specific  protective  inoculations  is  a  matter  of 
practical  importance.  This  result  of  experi- 
ment is  in  full  accord  with  clinical  experience 
which  has  shown  that  an  attack  of  diphtheria 
confers  little  or  no  immunity.  Although  it 
is  generally  possible  to  bring  about  some  small 
degree  of  immunity  with  diphtheria  serum 
the  immunization  does  not  necessarily  have 
anything  to  do  with  the  presence  of  special 
anti-substances.  The  slight  protective  effect 
that  has  been  observed  might  arise  from  the 
fact  that  when  old  cultures  are  used  we  intro- 
duce into  the  animal  besides  the  poisons  other 
bacterial  cell-substances  which  are  capable  of 
producing  immunity ;  or  it  may  be  that  the 
effect  is  caused  simply  by  another  sort  of  action 
due  to  the  suitable  stimulative  action  of  a 
sufficiently  active  chemical  body. 

In  line  with  Behring's  conception,  R.  Pfeif- 
fer  has  prepared  a  curative  serum  against 
typhoid  fever  by  inoculation  of  animals  with 
typhoid  bacteria.  Marmorek,  also,  who  ob- 
tained very  virulent  cultures  of  streptococci  by 

•...}  :»*  noli 


IMMUNITY.  357 

adding  human  blood  serum  to  bouillon  and 
with  these  brought  about  a  condition  of  high 
immunization  or  tolerance  of  poison  employed 
the  serum  of  animals  immunized  in  this  fashion 
to  protect  against  streptococcus  infections. 
These  streptococci  are  the  germs  of  puerperal 
fever  and  erysipelas,  and  are  also  especially 
concerned  in  the  septic  conditions  of  diph- 
theria. The  streptococcus  serum  therefore 
supplements,  as  it  were,  the  diphtheria  serum 
in  complicated  cases  and  mixed  infections. 
These  investigations  are  just  beginning  to  be 
taken  up  scientifically,  and  are  in  part  still  in 
the  advertisement  stage ;  we  shall  have  to  sub- 
mit to  many  a  serum  before  connection  is  again 
made  with  scientific  investigation. 

Phagocytes  and  Alexius — Antitoxic  and  Bac- 
tericidal Substances  in  the  Blood. 

Up  to  this  point  we  have  considered  only 
the  subject  of  "  specific  "  immunizations  and 
the  establishment  of  habituation  to  poisons. 
These  phenomena  seem  to  present  a  funda- 
mental contrast  to  those  of  natural  resistance 
or  immunity.  H.  Buchner,  especially,  has 
laid  great  stress  upon  this  contrast,  In  na- 
tural immunity  there  exists  only  the  specific 
ability  of  the  body  to  cope  with  definite  para- 
sites and  their  poisons  ;  in  "  specific  "  irnmu- 


BACTERIOLOGY. 

nization,  however,  a  "  specific  "  something  is 
added  by  the  "  specific  "  parasites. 

The  existence  of  this  essential  difference 
can  be  properly  attested  only  by  experiment. 
Fowls  which  are,  by  nature,  immune  to  teta- 
nus do  not  possess  in  their  blood  any  anti- 
substance  which  destroys  the  tetanus  toxin, 
yet  these  animals  show  no  symptoms  of  the 
disease  when  they  are  injected  with  tetanus 
culture, .  Natural  "  specific  "  immunity  seems 
in  their  case  to  be  connected  with  some  general 
property  of  the  tissues,  in  contrast  to  artificial 
immunity  which  is  supposed  to  depend  upon 
the  presence  of  specific  anti-substances  in  the 
blood. 

In  the  first  place,  we  must  ask,  what  are  the 
facts  upon  which  we  base  our  conception  of  the 
protective  power  of  the  human  and,  in  general, 
of  the  animal  organism  ? 

As  a  matter  of  fact,  the  animal  body  ordi- 
narily possesses  the  ability  of  ridding  itself  of 
bacteria  and  their  toxins.  It  is  always  to  be 
borne  in  mind  in  this  discussion,  that  in  certain 
diseases  the  toxins,  and  in  others  the  bacteria 
themselves  play  the  more  prominent  part.  The 
fact  that  the  animal  organism  can  cope  with 
living  bacteria  was  observed  in  1864,  by  M. 
Traube  and  Gescheidlen.  These  investigators 
introduced  putrefactive  bacteria  into  the  blood, 


IMMUNITY.  359 

and  noted  that  after  a  very  short  time,  the 
germs  had  entirely  disappeared.  The  eminent 
naturalist  Metschnikoff ,  has  since  urged  with 
great  vigor  the  view  that  the  wandering  cells 
of  the  body,  known  as  the  white  blood-cells  or 
pus  corpuscles,  betake  themselves  to  the  place 
threatened  by  the  bacteria,  where,  acting  as 
l(  devouring  cells  "  or  phagocytes,  they  engulf 
the  foreign  bacteria,  kill  and  digest  them  and 
thus  render  them  incapable  of  doing  harm. 
Certain  of  the  fixed  tissue  cells,  it  is  supposed, 
also  possess  this  power  of  phagocytosis.  It 
was  known,  some  time  ago,  that  the  wander- 
ing cells  possessed  the  power  of  taking  up  into 
themselves  lifeless  foreign  elements  found  in 
the  blood  and  of  removing  them  from  the  body- 
fluids,  thereby  making  and  keeping  the  blood 
and  lymph  channels  free  of  foreign  particles. 
There  arose,  consequently,  the  question  as  to 
whether  the  wandering  cells  generally  kill  the 
living  bacteria  or  whether  perhaps  other  in- 
fluences kill  the  bacteria,  and  the  wandering 
cells  merely  remove  the  lifeless  bodies,  just  as 
they  would  remove  other  foreign  bodies  for 
the  purpose  of  keeping  free  the  circulatory 
channels.  (See  frontispiece.) 

In  1884,  Grohmann  found  that  cell-free  blood 
destroyed  moulds  and  bacteria.  This  fact  was 
observed  afresh  by  Fodor,  in  1887,  and  has 


360  BACTERIOLOGY. 

been  confirmed  again  and  again  in  the  course 
of  manifold  and  varied  experiments.  It  was 
shown  by  Buchner  that  even  blood  that  has 
been  frozen,  and  in  which  the  wandering  cells 
have  consequently  been  rendered  wholly  im- 
potent, kills  bacteria  almost  as  quickly  as  fresh 
blood-serum.  On  the  other  hand,  blood  that 
is  warmed  to  6o°-7o°  loses  this  power.  From 
these  facts,  we  must  infer  that  the  blood- 
pla'sma  itself  is  able  to  kill  bacteria  in  a 
purely  chemical  way  ;  the  substances  in  the 
blood-plasma,  which  are  thus  effective  are 
the  so-called  "  active  proteids "  or  alexins. 
But  certain  of  these  active  chemical  protect- 
ive substances  are  also  able  to  neutralize 
the  bacterial  toxin,  as  we  may  conclude 
from  the  fact  that  if  active  blood-plasma  is 
brought  in  contact  with  bacterial  poisons 
outside  of  the  body,  the  poisonous  action  of  the 
latter  is  diminished  or  seems  even  to  be  com- 
pletely annulled,  whereas  in  the  same  blood  in- 
'side  of  the  organism,  chemical  combinations 
and  oxidations  or  other  transformations  may 
also  play  a  part  in  rendering  the  poisons  in- 
nocuous or  in  eliminating  them.  The  organ- 
ism possesses  in  the  peculiar  chemical  sub- 
stance known  as  nucleic  acid,  which  is  found  in 
the  cell  nucleus,  a  substance  that  kills  bacteria 
and  combines  with  basic  poisons.  A  similar 


•  IMMUNITY.  361 

action  perhaps  goes  on  in  the  intestine,  where 
the  peptones  of  digestion,  which  produce  a 
poisonous  effect  when  injected  directly  into 
the  circulation,  are  made  harmless  by  being 
converted  back  again  into  proteid  by  the  epi- 
thelium cells. 

The  organism,  therefore,  has  at  its  disposal 
certain  purely  chemical  aids,  variously  devel- 
oped in  the  various  organs,  tissues  or  cells, 
for  rendering  innocuous  the  foreign,  active  or 
ferment-like  soluble  poisons,  and  it  also  pos- 
sesses substances  in  solution  in  the  body- 
fluids,  which  are  able  to  weaken  parasites  and 
destroy  them. 

The  protective  power  of  the  blood  is  only 
manifested  plainly  outside  of  the  body  in  the 
cell-free  serum  ;  as  H.  Buchner  discovered,  it 
is  diminished  and  eventually  destroyed,  in 
proportion  to  the  amount  of  haemoglobin  with 
which  the  serum  is  mixed,  a  fact  which  ex- 
plains why  it  is  that  the  blood-poisoning  dis- 
eases are  so  likely  to  run  a  fatal  course.  Ac- 
cording to  Hankin,  the  protective  substances 
of  the  blood  serum  are  derived  from  the  leuco- 
cytes of  the  blood  ;  they  are,  so  to  speak, 
proteid  substances  made  active  through  the 
intervention  of  the  living  cells,  and  like 
the  enzymes  they  survive  the  cells  form- 
ing them.  Emmerich,  accordingly,  postu- 


362  BACTERIOLOGY. 

lates  the  existence  of  a  hypothetical  "  im- 
munizing proteid  "  (p.  332),  which  is  a  combi- 
nation of  such  active  leucocytic  proteid  with 
bacterial  proteid.  The  formation  of  such 
substances,  however,  is  advantageous  only 
when  kept  within  certain  limits.  If  too  many 
leucocytes  are  broken  up  so  that  a  cloudy  so- 
lution, rich  in  eosinophilous  granules  arises, 
then  such  a  serum,  which  when  originally 
possessed  of  a  merely  moderately  alkaline  reac- 
tion and  intact  leucocytes  could  kill  bacteria, 
may  become  through  the  steady  increase  in 
alkalinity  a  favorable  nutrient  medium  for 
bacteria  (Fischel).  Hence  we  may  find  con- 
nected with  the  state  of  the  serum  all  degrees 
of  bodily  condition  from  perfect  immunity  to 
a  high  predisposition  to  disease.-  During  the 
interchange  of  substances  in  cell  nutrition, 
other  active  proteid  bodies  may  pass  over  into 
the  serum  from  the  cells  and  tissues  of  the 
body,  and  so  by  the  indirect  participation  of 
those  cell  territories  which  are  concerned  in 
any  special  disease,  these  organic  elements  may 
be  a  factor  in  the  predisposition  to  disease, 
without  it  being  necessary  to  assume  that  any- 
thing of  a  foreign  nature  is  added  to  the  body. 
Within  the  body,  however,  blood  or  any 
body-fluid,  if  devoid  of  cells  exerts  no  defen- 
sive action.  MetschnikofI  discovered,  for  ex- 


IMMUNITY.  363 

ample,  that  in  septicaemia  processes  the  cell- 
free  aqueous  humor  of  the  eye — which  contains 
alexins — not  only  fails  to  kill  bacteria,  but  the 
bacteria  grow  in  the  fluid  luxuriantly  and  mul- 
tiply, whereas  they  die  off  in  the  blood  of  the 
same  animals,  when  it  contains  cells.  It  is 
possible  to  enclose  bacteria  in  permeable  mem- 
branes and  introduce  them  into  the  blood  or 
tissue  fluids.  When  this  is  done,  the  alexins 
that  are  present  in  solution  enter  the  mem- 
brane by  diffusion,  but  the  wandering  cells 
cannot  penetrate  it;  the  result  is  that  the 
parasites  grow  in  the  fluids,  although  these 
contain  alexin,  but  perish  in  the  blood  of  the 
same  animal  in  which  the  cells  are  present. 
Buchner  interprets  this  latter  occurrence  by 
the  supposition  that  in  such  experiments  the 
number  of  bacteria  introduced  is  too  insignifi- 
cant as  compared  with  the  quantity  of  the 
serum,  but  this  explanation  can  be  only  par- 
tially correct. 

Frequently  the  conditions  are  extraordinar- 
ily intricate,  so  that  it  is  difficult  to  distin- 
guish the  share  of  the  cells  from  that  of  the 
tissues.  When  a  local  disturbance  occurs  as 
the  result  of  parasitic  invasion,  then  a  reactive 
inflammation  with  the  formation  of  a  limiting 
wall  of  leucocytes  takes  place,  an  event  that 
must  be  considered  as  a  natural  healing  pro- 


364  BACTERIOLOGY. 

cess,  and  that  often  aids  in  recovery.  Ribbert 
asserts  that  this  surrounding  mantle  of  white 
blood-corpuscles  prevents  nutrient  material 
and  oxygen  from  reaching  the  bacteria,  but 
perhaps  also  the  white  blood-corpuscles  disin- 
tegrate, and  so  become  chemically  active  in 
the  way  pointed  out  by  Hankin.  In  all  such 
cases,  there  are  certain  stages  in  which  the 
parasites  in  the  foci  are  destroyed  without  be- 
ing first  taken  up  by  leucocytes.  Even  Met- 
schnikoff has  lately  admitted  some  such  indi- 
rect participation  on  the  part  of  the  leucocytes. 
According  to  R.  Pfeiffer,  if  we  inject  into  the 
peritoneum  of  a  guinea-pig  living  cholera  bac- 
teria suspended  in  bouillon  to  which  some 
cholera  serum  has  been  added,  a  remarkable 
alteration  of  the  bacteria  makes  its  appear- 
ance. They  become  changed  to  spherical 
structures,  a  transformation  which  R.  Pfeiffer 
looks  upon  as  a  kind  of  disintegration,  and  ex- 
plains as  an  accompaniment  of  death.  More 
-accurate  experiments  by  Metschnikoff  have, 
however,  resulted  in  suggesting  a  somewhat 
different  interpretation.  If  we  proceed  accord- 
ing to  Pfeiffer's  method,  a  disintegration  of  the 
leucocytes  immediately  follows  the  injection, 
and  this  disintegration  takes  place  among 
those  uninuclear,  polynuclear  and  eosinophil- 
ous  cells  which  Metschnikoff  looks  upon  as 


IMMUNITY.  365 

primarily  "  devouring  cells."  On  the  basis 
of  my  own  observations,  I  should  refer  this 
"  phagolysis,"  this  disintegration  of  the  leuco- 
cytes, to  the  action  of  the  foreign  active 
proteids  contained  in  the  serum,  since  I  have 
obtained  a  similar  result  with  enzymes.  The 
peritoneal  fluid  is  by  this  means  converted 
into  a  fluid  over-rich  in  active  proteid,  and  poor 
in  phagocytes.  Now  when  the  bacteria  are 
transferred  from  their  bouillon  into  such  a 
differently  constituted  fluid  they  attempt,  as  at 
all  times  when  some  injurious  influence  threat- 
ens the  species,  to  withdraw  themselves  from 
the  danger  by  passing  into  the  resting-stage, 
and  they  consequently  form  arthrospores. 
Metschnikoff  indeed  regards  these  spherules 
in  this  light,  and  they  do  indeed  appear  like 
true  arthrospores  (Fig.  196,  p.  36),  and  not 
like  comma  bacilli  which  have  undergone  de- 
generation (Fig.  9,  p.  19)  or  granular  disin- 
tegration (Fig.  10,  p.  20).  To  be  sure,  many 
of  these  spherules  die,  but  very  many  also  sur- 
vive and  really  preserve  the  existence  of  the 
species,  as  Metschnikoff  proved  through  ob- 
taining cultures  which  yielded  an  abundant 
growth,  a  result  which,  if  we  adopted  Pfeiffer's 
view,  would  not  be  expected  to  occur.  Later 
the  fluid  again  becomes  normal,  these  sphe- 
rules are  taken  up  by  leucocytes  and  only  then 


366  BACTERIOLOGY. 

lose  gradually  the  power  to  grow.  In  their 
intermediate  stages  also,  as  Metschnikoff  dis- 
covered, many  of  these  spherules  develop  again 
into  comma  and  screw  forms,  although  Pfeiffer 
supposed  development  to  be  impossible,  believ- 
ing that  the  germs  were  previously  destroyed 
by  the  body-fluids.  (Metschnikoff's  observa- 
tion, moreover,  agrees  in  part  with  the  observa- 
tions of  F.  Fischel,  so  far  as  experiments  which 
were  conducted  so  very  differently  can  be  di- 
rectly compared.)  The  leucocytes,  retiirning 
after  a  time,  take  up  in  this  second  stage 
both  the  comma  and  screw  forms  and  gradu- 
ally destroy  them.  We  know  that  the  germs 
are  taken  up  by  the  leucocytes  while  they  are 
still  in  a  living  condition,  and  not  after  they 
have  already  been  killed  by  the  body-fluids, 
from  the  fact  that  the  bacteria  germinate  in 
cultures.  The  body-fluids  therefore,  in  spite 
of  what  at  first  glance  has  the  opposite  appear- 
ance, are  not  able  to  destroy  the  comma  bacilli 
without  the  help  of  the  cells.  The  effective 
agent  in  the  fluids  according  to  Metschnikoff 
is  the  active  proteid  afforded  by  the  leucocytes 
(Hankin)  and  not  a  derivative  of  the  peritoneal 
endothelium  as  R.  Pfeiffer  supposed.  Metschni- 
koff was  able  to  bring  about  the  same  result  in 
a  test-tube  experiment  by  adding  leucocytes  to 
a  bouillon  culture  of  comma  bacilli  mixed  with 


IMMUNITY.  367 

cholera  serum.  We  may  infer  that  it  is  the 
leucocytes  and  the  substances  derived  from 
them  which  effect  the  change  of  the  comma 
bacilli  into  granules,  from  the  fact  also  that 
the  ;ame  sort  of  disintegration  takes  place 
within  the  leucocytes.  If  bouillon  be  injected 
into  the  peritoneum  before  the  injection  of  the 
bacteria  mixed  with  serum,  the  disintegration 
of  the  leucocytes  does  not  take  place,  but  pha- 
gocytosis of  the  bacteria  immediately  begins 
and  the  germs  are  in  part  transformed  into 
spherules  inside  of  the  phagocytes.  One  point 
appears  certain,  and  is  in  accord  with  Hankin's 
observation,  namely,  that  at  least  those  active 
proteid  bodies  of  the  serum,  which  apparently 
arise  from  the  white  blood-corpuscles  included 
under  the  term  phagocytes,  are  able  to  exert  a 
damaging  effect  upon  micro-parasites,  and  that 
therefore  the  condition  of  the  body-fluids  is  not 
in  every  case  a  matter  of  indifference.  But 
such  a  condition  of  the  fluids  really  depends 
upon  the  influence  of  the  cells. 

The  bactericidal  substance,  therefore,  which 
constitutes  the  protective  substance  or  alexin 
of  the  blood  plays  an  important  part  in  the  liv- 
ing body,  but  it  is  only  one  of  the  manifesta- 
tions of  phagocytic  activity,  since  it  is  possible 
by  means  of  specially  devised  experiments  to 
suppress  this  chemical  bactericidal  action  with- 


368  BACTERIOLOGY. 

out  altering  the  final  result.  The  body-cells 
which  by  virtue  of  their  specific  and  constant 
qualities  convert  the  nutritive  proteid  into  ac- 
tive proteid,  thus  bestowing  upon  it  their  own 
peculiarities  which  it  in  turn  communicates  to 
the  fluids,  are  the  factors  of  chief  importance. 
Behring's  doctrine  of  humoral  pathology,  that 
mysterious  doctrine  of  the  all-importance  of 
the  body  fluids,  which  virtually  ignores  the 
cells,  is  a  dogma  vindicated  by  no  sort  of  satis- 
factory experiment.  The  bactericidal  active 
proteid  substance  that  is  found  in  cholera 
serum  is  certainly  not  an  anti-substance 
against  the  cholera  toxin  (R.  Pfeiffer)  ;  a  truly 
antitoxic  body  has  not  yet  been  found  in  the 
blood  after  cholera  inoculations,  in  spite  of  the 
statements  of  Behring  and  Ransom,  although 
the  occurrence  of  such  a  substance  is  not  im- 
probable.1 

The  protective  serum,  as  Behring  terms  it, 
certainly  contains  very  different  sorts  of  sub- 
stances. Doubtless  elements  of  the  specific 
parasites  enter  into  the  formation  of  the  anti- 
substances,  and  among  these,  perhaps,  actual 
protective  substances  exist,  but  along  with 
these,  and  in  greater  amount,  occur  those 
peculiar,  normal  active  chemical  bodies,  which 

1  Recent  experiments  show  the  existence  of  a  cholera  antitoxin. 
E.  O.  J. 


IMMUNITY.  369 

have  been  rendered  active  and  brought  into 
solution  through  the  stimulus  of  a  foreign  pro- 
teid,  and  which  in  general  act  germicidally  or 
antidotally. 

Now  C.  Frankel  and  Sobernheim  have 
as  a  matter  of  fact  shown  that  by  heating 
protective  serum  to  70°  the  bactericidal  and 
antitoxic  substances  are  destroyed,  while  the 
serum  continues  to  exert  a  protective  effect. 
The  anomaly  may  be  only  apparent,  and  due 
to  overhaste  in  generalization.  The  physical 
participation  of  the  tissue-cells,  of  the  wander- 
ing-cells, and  of  other  mechanical  aids,  and  also 
the  share  of  the  chemical  protective  substances 
of  the  blood  (alexins)  and  of  other  chemical  in- 
fluences may  be  developed  in  different  degrees 
in  individual  cases,  and  may  manifest  their 
activity  differently  according  to  the  mode  of 
attack  of  the  parasites ;  just  as  the  parasites 
themselves  sometimes  produce  their  effect 
chiefly  through  their  multiplication,  sometimes 
chiefly  through  formation  of  poison. 

In  every  case  the  human  organism  possesses 
within  itself  powerful  means  of  defence,  both 
cellular  elements  and  chemical  substances. 
The  latter  are  derived  directly  or  indirectly 
both  from  the  stationary  tissue-cells  and  the 
motile  wandering  cells  ;  these  chemical  sub- 
stances enable  the  organism  to  cope  with  sap- 
24 


3/0  BACTERIOLOGY. 

rophytes  and  also  with  parasites  and  their 
poisons.  This  power  is  in  itself  nothing  pe- 
culiarly "  specific,"  bnt  only  specific  to  the  ex- 
tent that  we  are  in  general  able  to  distinguish 
species  and  races,  organs  and  tissues.  In  this 
general  sense  some  species  of  microbes  are  able 
to  enter  into  close  relations  with  man,  while 
others  only  sustain  relations  more  remote  and 
others  none  at  all.  Seemingly  qualitative 
deviations  are  often  only  quantitative  modifi- 
cations of  some  of  the"  fundamental  activities 
that  are  common  to  all  cells.  The  qualitative 
aspect  is  at  bottom  merely  due  to  an  accom- 
modation of  our  ideas  to  the  subjective  limits 
of  our  knowledge  just  as  we  anthropocentric- 
ally  distinguish  light  and  electricity,  tubercu- 
losis and  diphtheria,  without '  any  intrinsic 
necessity.  If  this  is  kept  in  mind  there  can 
be  no  great  harm  in  asserting  that  the  natural 
resistance  of  man  to  disease-producing  bacteria 
has  a  "  specific  "  character,  that  it  exists  as  a 
natural  endowment  protecting  against  certain 
species  of  parasites  and  not  against  others.  It 
is  another  expression,  a  different  statement  of 
the  well-known  fact. 

As  compared  with  this  condition,  "  speci- 
fic "  immunization  presents  further  problems. 
Metschnikoff  has  found  that  before  animals 
have  received  a  protective  inoculation  against 


IMMUNITY.  371 

anthrax,  the  wandering  cells  of  the  uninocu- 
lated  animal  do  not  take  up  the  anthrax  bacilli 
and  the  same  is  true  of  some  other  diseases  ; 
after  the  protective  inoculation,  however,  they 
all  do  this,  and  in  each  individual  instance  the 
protective  activity  thus  acquired  by  the  wan- 
dering cell  is  manifested,  it  is  claimed,  only 
against  the  one  disease,  and  is  therefore  iso- 
pathic  or  "  specific."  The  bacteria  taken  up 
by  the  phagocytic  cells  are  not  always  digested, 
however,  and  may  sometimes  multiply  in  the 
cells  and  at  their  expense,  a  phenomenon  that 
is  often  to  be  seen  in  swine-erysipelas,  leprosy 
and  tuberculosis.  In  the  latter  disease  wan- 
dering white  blood-corpuscles  freighted  with 
tubercle  bacteria  may  distribute  the  parasites 
over  the  body,  and  so  lead  to  general  infection. 
But  facts  of  this  sort  prove  also  that  cells  are 
able  to  take  up  into  themselves  living  and  fully 
virulent  bacteria  ;  they  confirm  therefore  the 
contention  of  the  phagocyte  theory. 

According  to  Behring  the  tissues  form  the 
anti-substances  very  slowly  in  the  process  of 
"active"  immunization.  But  this  notion  is 
wholly  incorrect.  I  have  already  shown  that 
the  formation  of  anti-substances  is  only  an  in- 
cidental and  not  a  causal  and  necessary  ac- 
companiment of  immunity.  Immunity  may  be 
brought  about  and  yet  these  antagonistic  sub- 


3/2  BACTERIOLOGY. 

stances  be  altogether  wanting.  The  more  im- 
portant factors  are  the  active  proteid  bodies 
that  are  always  present  in  the  blood  and  tissue 
juices.  These  fluids  are,  however,  dependent 
for  their  peculiar  qualities  upon  the  peculiar 
qualities  of  the  cell-territories,  and  the  "  speci- 
fic "  substances  stimulate  just  those  cell  terri- 
tories which  are  of  special  importance  for  the 
individual  diseases. 

Effectual  protective  inoculation  and  habitu- 
ation  to  poison  come  about  only  through 
the  intervention  of  the  body-cells,  which  are 
stimulated  to  one  of  the  infinitely  various  ac- 
tivities made  possible  by  their  complicated 
structure,  and  which  are  prompted  by  the  stim- 
ulus, to  a  mode  of  action  differing  only  quan- 
titatively from  their  normal  activity,  although 
the  action  is  seemingly  of  a  qualitative  char- 
acter and  unprovided  for  in  the  physiological 
organization.  The  effect  thus  produced  out- 
lasts the  transitory  stimulus,  because  it  is 
bound  up  with  the  permanent  and  independent 
cellular  elements  of  the  body.  The  retention 
of  the  newly-acquired  property  depends  upon 
the  condition  of  the  body,  and  upon  the  kind 
of  stimulating  substance  and  its  manner  of 
introduction;  the  more  profound  the  stimulus, 
the  more  durably  does  it  impress  itself  upon 
the  organism,  and  the  better  is  it  fitted  for  in- 


IMMUNITY.  373 

terfering  with  the  usual  energetical  processes 
of  the  body-cells.  Viewed  in  this  aspect,  the 
"  specific  "  bodies  are  as  a  rule  best  suited  for 
attaining  the  desired  end,  but  since  their  spe- 
cificity is  not  due  to  an  ability  to  effect  a  neu- 
tralization of  molecule  by  molecule,  other  bod- 
ies also  must  be  able  to  interfere  in  the  same 
way  and  to  influence  the  same  "  specific  "  cell 
territories.  Even  the  passive  protective  in- 
oculations are  not  entirely  dependent  upon 
the  mere  addition  of  chemical  substance  to  the 
blood  serum,  but  owe  their  influence  to  a 
stimulus  to  the  cells  and  a  corresponding  re- 
action on  the  side  of  the  cells,  and  hence  in 
reality  they  also  are  active. 

The  distinction  between  active  and  passive 
inoculation  is  only  a  quantitative  one,  and  both 
kinds  of  immunity  result  from  the  action  of 
"  specific  "  stimulating  substances  upon  the 
body-cells  and  the  reaction  of  the  cells  to  these 
stimuli.  The  "  exhaustion  hypothesis  "  first 
propounded  by  Klebs  and  Pasteur,  according 
to  which  certain  substances  occurring  in  the 
organism  of  the  host  and  necessary  to  the  life 
of  the  micro-parasite  are  exhausted  by  the 
growth  of  the  parasite,  thus  rendering  the  host 
an  unsuitable  culture  medium  is  untenable. 
The  "  retention  hypothesis, "  put  forward  by 
Chauveau,  which  supposed  that  metabolic 


374  BACTERIOLOGY. 

products  accumulate  in  the  body  of  the  host 
and  are  injurious  to  the  bacteria  forming  them 
in  the  way  that  lactic  acid  is  injurious  to  the 
lactic  acid  bacteria,  or  alcohol  to  the  yeast  cell, 
is  in  a  restricted  sense  correct,  and  agrees 
with  what  we  know  of  the  formation  of  anti- 
substances,  but  the  hypothesis  itself  has  no 
special  significance. 

The  distinction  between  natural  immunity 
and  artificial  immunity  can  no  longer  be  main- 
tained. In  both,  the  wandering  cells  may  be 
able  to  take  up  parasites.  Even  in  naturally 
immune  animals,  anti-substances  may  at  times 
be  present.  Abel  has  found  sometimes  present 
in  the  blood  of  healthy  men  an  anti-substance 
that  protects  against  the  diphtheria  toxin; 
Stern  has  found  one  protecting  against  the 
germ  of  typhoid  fever,  and  MetschnikofT  one 
against  cholera,  and  on  the  other  hand,  as  al- 
ready mentioned,  animals  that  are  specifically 
immunized  against  these  diseases,  may  not  pos- 
sess any  anti-substances  in  their  serum. 

The  conditions  of  hyper-immunity,  natural 
immunity  and  artificial  immunity  are  all  resi- 
dent alike  in  the  cells  and  tissues  of  the  body. 
The  wandering  cells  of  an  animal  may  be  en- 
dowed from  the  outset  with  special  voracity  or 
they  may  acquire  this  property,  for  the  wander- 
ing cells,  of  course,  are  both  directly  and  indi- 


IMMUNITY.  375 

rectly  dependent  upon  the  condition  of  the 
whole  body.  The  tissue  juices  also  are  able  to 
interpose  in  the  contest,  by  virtue  of  the  active 
proteid  substances  they  contain.  That  very 
quality,  however,  which,  according  to  Behring, 
is  the  cardinal  one,  namely,  the  possession  of 
anti-substances,  the  very  character  wherein  the 
"  specificity  "  of  the  parasite  is  most  sharply 
expressed,  appears  to  be  of  secondary  signifi- 
cance. The  anti-substances  are  frequently 
absent  where  immunity  exists,  and  their  pres- 
ence or  absence  is  without  regularity.  This 
fact  helps  to  perplex  us  still  more  about  the 
phenomenon  of  "  specificity,"  so  far  as  "  spe- 
cificity "  is  looked  upon  as  an  explanation  of 
the  real  heart  of  the  matter,  or  the  " specific" 
microparasite  is  regarded  as  the  exclusive  factor 
in  the  production  of  immunity.  Where  Behr- 
ing and  Pf eiffer  speak  of  the  specificity  of  para- 
sites and  anti-substances  it  is  more  correct  to 
speak  simply  of  the  activity  of  body  cells  and 
fluids. 

If  stimuli  act  upon  a  normal  physiological 
condition  that  exists  as  a  momentary  adapta- 
tion or  upon  a  condition  of  health  regained 
after  a  complete  cure,  the  stimuli  that  some- 
times effect  protection  and  cure  may,  by  repe- 
tition, bring  about  at  times  a  more  ready 
discharge  of  energy  (as  we  witness  in  the 


3/6  BACTERIOLOGY. 

"  learning  "  of  physiological  stimuli),  and  the 
irritability  or  disease  predisposition  is  height- 
ened. This  is  what  happens  in  rheumatism, 
catarrh,  influenza,  pneumonia  and  diphtheria. 
Or  it  may  be  that  the  resistance  to  a  discharge 
of  energy  is  increased  as  the  result  of  adapta- 
tion, and  thus  an  habituatl*on  to  the  stimulus 
makes  its  appearance,  so  that  the  same  stimulus 
is  no  longer  able  or  is  less  easily  able  to  cross 
the  physiological  threshold  and  cause  reaction. 
The  degree  of  resistance  not  only  varies  greatly 
in  different  diseases,  but  even  in  different  in- 
dividuals towards  the  same  disease.  There  are 
some  men  who  become  ill  through  vaccination, 
and  others  who  gain  through  vaccination  no 
immunity  whatever  against  small-pox.  Only 
a  slight  immunity  is  acquired  as  the  result  of 
an  attack  in  some  diseases,  as,  for  instance,  in 
tetanus  and  cholera. 

A  part  only  of  the  "  specific  "  curative  in- 
oculations— possibly,  for  example,  Pasteur's  in- 
oculation against  rabies — are  to  be  conceived 
as  anticipatory  protective  inoculations.  The 
action  of  the  anti-substances  in  serum  therapy, 
especiall}7,  shows  that  some  of  these  cures  by 
injection  have  nothing  to  do  with  protective 
inoculation  and  depend  simply  upon  the  effect 
of  one  active  body,  the  antitoxin  or  the  prc- 
teid  of  the  serum,  on  another  active  body,  the 


IMMUNITY.  377 

toxin  ;  the  brief  immunity  that  accompanies 
the  cure,  results  from  stimulation  of  the  natu- 
ral defensive  forces  of  the  organism,  and  from 
the  rendering  of  these  forces  active,  and  is  an 
accessory  phenomenon  which  does  not  con- 
tribute to  the  cure.  Such  curative  effect  as 
we  strive  to  obtain  with  serum,  and  do  obtain 
in  such  very  different  degrees,  must  be  much 
more  general  in  character  than  that  obtained 
by  "  specific  "  antidotes  against  "  specific  " 
poisons,  and  can  be  brought  about  in  a  far 
simpler  way.  Even  in  those  cases  in  which 
we  are  unwilling  to  relinquish  the  specific  dis- 
ease germs  as  the  starting-point  in  our  quest 
for  a  curative  substance,  we  may  well  find 
some  way  to  spare  ourselves  the  time-robbing, 
expensive  and  circuitous  route  through  the 
body  of  animals. 

Are   There  Protective  and  Curative  Inocula- 
tions That  Are  Non-Specific  ? 

It  was  shown,  in  1889,  by  Woodhead,  Wood 
and  Hueppe  that  it  is  possible  to  immunize 
animals  against  anthrax  by  inoculating  them 
with  the  bacillus  of  green  pus  (B.  pyocyaneus), 
and  its  metabolic  products.  It  was  then  shown 
by  Hueppe,  and  confirmed  by  Klein  and 
Sobernheim,  that  it  is  possible  to  immunize 
animals  against  cholera  by  employing  many 


BACTERIOLOGY. 

different  kinds  of  bacteria  and  bacterial  pro- 
ducts, and  it  was  at  once  recognized  that  the 
basis  for  this  result  lay  in  the  rendering  active 
both  of  the  ordinary  cellular  defensive  elements 
of  the  body  and  of  those  chemical  elements  that 
have  gone  into  solution,  although  Klein  er- 
roneously supposed  that  the  bacteria  employed 
in  these  experiments  form  the  same  poison  as 
that  formed  by  the  cholera  germ  and  bring 
about  their  protective  effect  by  causing  an 
habituation  to  their  poison.  These  first  ex- 
periments were  prompted  by  certain  unex- 
pected results  of  investigation.  The  discovery 
was  made  that  if  we  introduce  into  cultures  of 
parasitic  bacteria  micro-organisms  of  a  different 
sort,  as,  for  instance,  the  bacilli  of  blue-green 
pus  into  cultures  of  anthrax  bacteria,  the  latter 
grow  more  feebly.  These  experiments  belong 
in  the  class  of  antagonistic  effects  described 
on  p.  119.  In  such  cases,  there  could  be  no 
question  of  any  "  specific  "  protective  inocula- 
tion or  of  any  adaptation  to  a  specifically  iden- 
tical material  from  the  cultures,  or  of  any 
habituation  to  the  presence  of  the  same  sort  of 
foreign  protoplasm  or  to  a  similar  poison.  In 
the  course  of  various  attempts  made  to  bring 
about  the  cure  of  bacterial  diseases  in  this  way 
we  gradually  learned  to  see  that  the  effects 
produced  depend  upon  the  excitation  of  an  in- 


IMMUNITY.  379 

flammation,  and  hence  upon  a  stimulation  of 
the  cell  territories  already  seized  by  the  bac- 
teria or  involved  in  the  invasion. 

After  it  had  been  discovered  by  Nageli, 
Pasteur  and  Koch,  and  still  more  precisely  by 
Emmerich,  Freudenreich,  Woodhead,  Wood 
and  Hueppe  that  some  pathogenic  bacteria  are 
destroyed  in  cultures  by  saprophytic  bacteria, 
the  attempt  was  made  to  effect  a  cure  by  in- 
corporating such  saprophytes  into  the  body  of 
previously  infected  animals.  Clinical  experi- 
ence afforded  some  justification  for  this  pro- 
cedure, as  for  instance  in  the  observations  that 
cancerous  tumors  degenerate  if  the  bacterial 
disease  of  erysipelas  makes  its  appearance  at 
the  diseased  locality,  and  that  the  sickening 
odor  of  a  cancer  may  abate  and  even  cease 
when  bandages  wet  with  a  lactic  acid  fermen- 
tation are  applied.  Cantani,  by  his  use  against 
tuberculosis  of  bacteria  of  putrefaction  was  the 
first  to  employ  such  a  "  bacterio-therapy." 
Animal  anthrax  was  more  satisfactorily  com- 
bated by  Emmerich,  di  Mattei  and  Paul- 
owski,  by  use  of  the  living  bacteria  of  erysipe- 
las or  the  microbe  of  the  bleeding-host  (B. 
prodigiosus),  and  by  Bouchard,  Woodhead  and 
Wood  by  use  of  the  bacteria  of  green  pus.  Up 
to  the  present,  therefore,  we  have  attempted  to 
imitate  two  natural  methods  of  producing  im- 


380  BACTERIOLOGY. 

munity,  first,  the  isopathic,  or  homeopathic, 
that  is,  the  prevention  of  infectious  diseases 
through  inoculation,  after  the  manner  of  vacci- 
nation against  small-pox,  and  second  the  an- 
tagonistic or  allopathic,  the  utilizing  of  the 
antagonistic  action  of  different  species  of  bac- 
teria in  their  struggle  for  food. 

The  experiments  upon  antagonism  which 
were  made  with  living  bacteria  were  repeated 
by  the  same  observers  with  the  metabolic 
products  of  the  germs.  The  result  was  the 
same,  both  for  protective  and  curative  pur- 
poses. 

Romer  was  the  first  to  prove  that  it  is  pos- 
sible in  dealing  with  animal  tuberculosis  to 
obtain  the  same  success  with  the  use  of  the 
proteids  of  other  bacteria  as  was  gained  with 
tuberculin.  Along  the  same  line,  C.  Frankel 
attempted  to  influence  favorably  the  course  of 
typhoid  fever  by  use  of  the  proteids  of  the 
typhoid  bacteria,  and  Rumpf  achieved  the 
same  result  with  the  proteids  of  the  bacteria 
of  green  pus,  while  other  proteids  did  not  work 
so  well.  Since  these  experiments  were  carried 
out  upon  man,  I  will  briefly  set  forth  the 
results  so  far  as  the  statements  permit  of 
comparison. 

Frankel  recorded  among  60  cases  of  typhoid 
fever,  5  deaths  or  8.3  per  cent.,  Rumpf  among 


IMMUNITY.  381 

only  30  cases  2  deaths,  or  6.6  per  cent.,  while 
Glaser's  statement  regarding  3285  cases,  from 
1869-1877,  without  specific  treatment,  showed 
a  mortality  of  7.5  per  cent.,  with  a  minimum 
of  5  per  cent,  and  a  maximum  of  9.6  per  cent. ; 
in  the  general  hospital  at  Hamburg  between 
1882-1891,  the  fatality  was  2298  among  25,824 
patients,  or  8.9  per  cent,  with  a  minimum  of 
6  per  cent.  (1887)  and  a  maximum  of  19  per 
cent.  (1882).  How  far  larger  numbers  would 
affect  for  the  worse  the  results  of  Frankel 
and  Rumpf  we  can  not  conjecture  since  the 
above  data  were  communicated  before  the  ter- 
mination of  all  the  cases.  The  only  conclusion 
that  can  be  fairly  drawn  therefore,  is  that  it  is 
possible  to  inject  both  isopathic  and  antagonis- 
tic substances  into  typhoid  patients.  Whether 
it  is  possible  to  bring  about  a  cure  by  this 
method  is  still  wholly  uncertain ;  in  any  case 
the  same  result  was  achieved, — probably  even 
a  better  result, — without  use  of  any  of  these 
remedial  substances  and  therefore  without  risk 
of  doing  injury. 

The  proteids  bring  about  their  effect  (as 
shown  on  p.  180)  in  a  general  way,  by  excit- 
ing inflammation  in  the  tissues  invaded  by  the 
microparasites.  H.  Buchner  has  proved  also 
by  researches  made  upon  the  action  of  arsenic 
that  the  reactions  of  the  human  body  taking 


382  BACTERIOLOGY. 

place  in  the  form  of  inflammations  can  be 
made  serviceable  for  curative  purposes  without 
there  being  anything  specific  about  the  pro- 
cess. In  the  chapter  upon  the  healing  of 
disease  in  general,  I  have  already  men- 
tioned the  fact  that  by  evoking  similar  re- 
actions from  the  body  through  the  use  of 
physical  agents,  it  is  possible  to  arouse  to  tem- 
porarily exalted  activity  the  natural  protective 
forces  residing  in  the  local  cells,  the  wandering 
cells  and  the  active  chemical  bodies  of  the  tis- 
sue fluids.  In  the  same  way  the  rise  of  bodily 
temperature,  if  it  does  not  overstep  certain 
limits  may  have  a  good  effect  upon  the  course 
of  the  disease,  and  the  idea  of  the  older  phy- 
sicians who  regarded  fever  and  inflammation  as 
the  healing  efforts  of  nature,  may  thus  in  the 
light  of  experiment  turn  out  to  be,  to  a  certain 
extent,  correct.  The  old  view  that  an  excre- 
tion of  the  "  materia  peccans  "  takes  place  by 
means  of  the  kidneys,  intestine  and  stomach 
is,  likewise  to  be  regarded  as  correct  within 
certain  limits  (p.  202).  All  symptoms  of  this 
character  are  the  outward  signs  of  a  nat- 
ural and  necessary  reaction  towards  an  im- 
pulse that  tends  to  liberate  energy.  Symp- 
toms in  themselves  may  be  either  good  or 
bad.  How  far  they  are  actually  beneficial  or 
injurious  depends  upon  the  point  of  view 


IMMUNITY.  383 

or  upon  the  special  circumstances  of  the 
case. 

Starting  from  the  idea  of  antagonism  and 
from  the  clinical  observation  that  morbid 
tumors  are  favorably  affected  by  an  outbreak 
of  erysipelas,  Emmerich  and  Scholl  have 
made  animals  immune  against  streptococci, 
and  have  attempted  to  cure  anthrax,  tuber- 
culosis, sarcoma  and  cancer  with  the  serum 
of  these  animals.  While  Emmerich  and 
Scholl  obtained  good  results  in  their  experi- 
ments upon  man,  other  clinicians  who  have 
worked  with  this  serum  have  up  to  the  present 
time  not  met  with  success. 

With  a  more  precise  analysis  of  the  facts, 
then,  it  appears  that  the  specific  serum  con- 
taining the  antitoxin  does  not  cure  because  it 
immunizes,  but  that  it  cures  in  spite  of  its  not 
immunizing.  The  serum  cure  is  not  a  sort  of 
rapid  immunization,  but  is  based  solely  on  the 
fact  that  strongly  active  bodies  present  in  the 
curative  serum  act  antitoxically  or  bactericid- 
ally,  and  hence  display  in  an  exalted  degree 
an  activity  which  we  find  exists  also  as  a  gen- 
eral capacity  of  the  normal  healthy  serum  of 
all  animals,  although  developed  in  different 
ways  according  to  the  species.  There  is,  in 
fact,  between  the  antitoxic  and  bactericidal 
power  of  the  normal  serum  which  is  deter- 


384  BACTERIOLOGY. 

mined  by  the  species  of  host-organism,  and 
the  same  property  of  the  serum  which  has 
been  acquired  or  heightened  by  specific  im- 
munization or  habituation  to  poison,  not  a 
qualitative  but  merely  a  quantitative  distinc- 
tion. The  stimulus  that  produces  a  state  of 
immunization  and  habituation  to  poison  has 
the  visible  effect  of  increasing  the  quantity  of 
active  bodies  in  the  blood  serum.  Only  seem- 
ingly in  this  case  has  a  new  qualitative  char- 
acter been  added,  for  the  bacterial  components 
found  in  the  curative  serum  have  nothing  to 
do  with  the  antitoxic  effect.  The  bacterial 
substance  constitutes  merely  the  special  form 
of  stimulus  and  may  be  altogether  absent  with- 
out any  change  in  the  result  if  only  in  some 
way  or  other  there  is  provided*  some  sort  of 
stimulus  which  induces  the  specific  cell  terri- 
tories and  cells  of  the  host  to  generate  suf- 
ficient quantities  of  the  active  bodies. 

The  bacterial  component, — and  this  can  be  re- 
garded as  the  sole  specific  element, — is  certainly 
not  essential  to  the  formation  of  the  antitoxin 
as  is  seen  from  the  following  experiments, 
which  in  great  part  we  owe  to  Roux  and  his 
pupils  Calmette,  Phisalix  and  Bertrand. 

i.  The  normal  serum  of  healthy  warm- 
blooded animals  acts  in  vitro  upon  specific  tox- 
ins just  as  if  it  contained  specific  antagonistic 


IMMUNITY.  385 

substances.  The  blood  of  healthy  men  in 
many  cases  neutralizes  the  diphtheria  toxin 
(Abel),  the  typhoid  toxin' (Stern),  and  the  toxin 
of  cholera  (Metschnikoff),  while  it  has  no  effect 
upon  tetanus  toxin,  snake  venom  and  abrin. 
(From  the  first  observation,  Wassermann  has 
drawn  the  far  too  hasty  conclusion  that  in  such 
cases  the  healthy  individuals  had  previously 
resisted  a  mild  attack  of  diphtheria.)  I  have 
called  attention  previously  (p.  183)  to  a  similar 
observation  of  Hericourt  and  Richet  to  the 
effect  that  the  serum  of  healthy  dogs  protects 
rabbits  against  staphylococcus  pyaemia. 

2.  Antitoxins  that  are  formed  specifically  in 
serum  act  in  vitro  upon  poisons  of  a  specific- 
ally different  character  in  the  same  manner  as 
upon  poisons  specifically  similar,  while  the  con- 
verse does  not  always  obtain  :  "  anti-venin  " 
annuls  the  poisonous  effect  of  abrin,  but  not  of 
diphtheria  toxin,  tetanus  toxin  or  ricin ;  aiiti- 
abrin  neutralizes  the  toxic  effect  of  snake 
venom,  diphtheria  toxin  and  ricin,  but  not  that 
of  tetanus  toxin ;  tetanus  antitoxin  is  antago- 
nistic to  snake  venom,  but  powerless  against 
ricin  and  abrin  ;  rabies  serum  is  potent  against 
snake  venom,  but  impotent  against  the  diph- 
theria and  tetanus  toxins,  and  against  ricin  and 
abrin;  streptococcus  serum  is  potent  against 
snake  venom,  powerless  against  the  others  ; 
25 


386  BACTERIOLOGY. 

cholera  serum  is  moderately  effective  against 
snake  venom,  but  without  effect  against  the 
others ;  diphtheria  antitoxin  is  powerless 
against  snake  venom,  tetanus  toxin,  ricin  and 
abrin ;  the  antitoxin  sera  of  swine-erysipelas 
and  typhoid  are  powerless  against  all  these 
poisons. 

3.  Within   the   animal   body,    also,  specific 
serum    anti-toxin    may  exert   an   effect  upon 
specifically  different  poisons.      The   serum  of 
animals  immunized  against  the  venom  of  any 
one  species  of  snake  protects  animals  against 
snake  venom  of  any  other  species  and  against 
scorpion  venom.     The  serum  of  animals  im- 
munized against  cobra  poison  renders  rabbits 
immune  to  abrin.     When  Marmorek  wished 
to  endow    animals  simultaneously    with   the 
antitoxin   protecting  against  diphtheria    and 
with  that  protecting  against  streptococci,  and 
for  this  purpose  injected  streptococci  into  horses 
which  Roux  had  previously  immunized  against 
-diphtheria,  the  animals  endured  the  treatment 

almost  without  reaction  while  animals  not  pre- 
viously treated  for  diphtheria  reacted  very  vig- 
orously ;  the  diphtheria  antitoxin,  therefore,  in 
the  body  of  the  animal  exerts  a  protective  ac- 
tion against  the  streptococci  and  their  toxin. 

4.  Antitoxins     which    in     vitro    neutralize 
specifically  similar  or  dissimilar  toxins   may 


IMMUNITY.  387 

be  without  effect  in  the  animal  body.  The 
civet-cat  is  immune  against  the  bite  of  a  ser- 
pent and  its  serum  is  antitoxic  against  snake 
venom,  so  that  the  reason  for  the  natural  toler- 
ance of  the  poison  might  be  thought  to  be  the 
possession  of  this  quality.  The  blood  of  the 
hedge-hog,  however,  which  is  likewise  immune 
against  snake  venom,  contains  also,  but  in  much 
slighter  amount,  an  antidote  against  the  snake 
venom.  Swine,  on  the  other  hand,  which  are 
also  immune  bear  in  their  serum  no  antitoxin 
against  snake  venom,  and  dogs,  which  do  suc- 
cumb to  snake  bite,  possess  in  their  blood  an 
antitoxin  against  snake  venom.  The  anti- 
toxin is  therefore  sometimes  present,  some- 
times absent,  sometimes  it  is  of  assistance  in 
protecting  an  animal,  sometimes  not.  Ani- 
mals immune  to  tetanus,  and  likewise  animals 
immune  to  abrin,  succumb  to  snake  venom,  in 
spite  of  the  fact  that  both  tetanus  antitoxin 
and  anti-abrin  paralyze  in  vitro  much  larger 
quantities  of  snake  venom  than  would  suffice 
to  kill  these  animals.  Diphtheria  serum 
mixed  with  abrin  retards  the  poisonous  effect 
of  the  abrin  in  the  animal. 

5.  A  serum  or  antitoxin  which  in  vitro  does 
not  act  upon  the  poison  may  yet  exert  an  an- 
tidotal or  curative  effect  when  injected  into  the 
body  of  the  animal.  Rabies  serum  does  not 


388  BACTERIOLOGY. 

immunize  animals  against  rabies,  but  does 
against  snake  venom.  The  serum  of  rabbits 
which  have  been  immunized  against  rabies 
protects  animals  against  cobra  venom  almost 
as  well  as  does  the  cobra  anti-venin  itself. 
Dogs,  however,  which  are  immunized  against 
rabies,  and  possess  a  serum  protecting  other 
animals  against  snake  venom  are  themselves 
susceptible  to  snake  venom.  On  the  other 
hand  rabbits  immunized  against  snake  venom 
have  become  resistant  towards  the  "  street- 
virus  "  '  of  rabies,  but  still  succumb  to  the 
more  virulent  rabies  of  rabbits. 

6.  A  protective  and  curative  effect  may  be 
wrought  without  the  specific  antitoxin.  Ani- 
mals immunized  for  abrin  are  immune  against 
anthrax  (Calmette).  Rabbits  immunized 
against  anthrax  are  relatively  immune  against 
abrin,  but  their  serum  contains  no  anti-abrin. 
The  fact  that  fowls  immunized  against  tetanus 
possess  no  tetanus  antitoxin  has  already  been 
mentioned.  The  antitoxin  that  is  present  in 
the  blood  after  immunization  is  therefore  at 
least  superfluous  for  purposes  of  protection. 

The  specificity  of  action  of  the  anti-sub- 
stances is  obviously  not  essential  to  their  anti- 
dotal effect,  and  it  is  therefore  not  necessary 
to  assume  it  in  a  causal  interpretation  of  im- 

1Therabic  virus  procured  from  dogs  which  is  of  a  constant  intensity. 


IMMUNITY.  389 

munity.  The  common  feature  in  all  cases  of 
immunity  of  this  sort  is  the  formation  of  active 
bodies  in  the  serum  of  the  immunized  animals 
by  means  of  the  stimulus  exerted  by  the 
poison  that  is  introduced,  and  it  is  the  action 
of  these  active  bodies  upon  the  active  poison 
that  causes  the  molecular  movement  of  the  lat- 
ter to  cease.  Sometimes  the  specific,  isopathic 
stimulus  of  the  same  nature  is  best  adapted  for 
thus  rendering  active  the  body-proteid,  and 
hence  is  in  a  sense  necessary,  but  sometimes 
a  heterogeneous  and  specifically  dissimilar,  or 
even  an  entirely  foreign  stimulus  is  sufficient. 
Although  the  results  of  the  experiments 
upon  man  are  still  in  dispute  the  results  ob- 
tained by  experiments  upon  animals  with 
specifically  different  bacteria,  metabolic  pro- 
ducts, proteids  and  sera  are  frequently  just  as 
favorable  as  the  results  obtained  by  isopathic 
and  homeopathic  treatment  with  specifically 
identical  or  closely  similar  material. 

For  protective  inoculation  and  healing,  ac- 
cordingly, isopathy  or  the  use  of  specific  dis- 
ease germs  and  their  metabolic  products  is  not 
essential;  the  same  results  can  be  reached 
with  other  bacteria.  But  probably  it  is  not 
essential  that  bacteria  or  bacterial  products 
be  employed  for  this  purpose.  In  experiments 
upon  animals  I  succeeded  in  the  case  of  two 


390  BACTERIOLOGY. 

diseases,  pneumonia  and  cholera,  in  influenc- 
ing favorably  the  course  of  the  disease  by  other 
active  bodies,  and  in  curing  entirely  without 
the  use  of  chemical  substances  of  this  class. 


Protective  and  Curative  Inoculations  Without 
the  Use  of  Microparasites  or  Their  Products. 

Immunity  may  certainly  in  some  cases  be 
obtained  by  other  methods  of  treatment. 
Wooldridge  in  1888  prepared  from  the  thymus 
gland  of  the  calf  and  from  other  tissues  proteid 
bodies  in  the  form  of  "  tissue  fibrinogen  "  with 
which  he  obtained  immunity  against  anthrax  ; 
this  sort  of  immunity  probably  depends  upon 
increased  leucocytosis  and  the  phagocytic  ac- 
tion thus  made  possible.  Upon  this  action  of 
the  thymus  proteids  also  depends  the  fact  that 
cultures  of  pathogenic  bacteria  grown  in  thy- 
mus bouillon  are  at  times  impotent.  (Brieger, 
Kitasato  and  Wassermann  thought  that  the 
thymus  removed  the  toxic  quality  of  the  cul- 
tures, but  this  is  not  the  case.)  I  myself  was 
able  to  confer  immunity  against  cholera  by  use 
of  the  digestive  ferments.  Soluble  active  sper- 
min  in  an  alkaline  medium  is  able  to  immunize 
for  the  reason  that  it  evokes  a  favorable  leu- 
cocytosis (Poehl).  If  the  formation  of  insolu- 
ble active  spermin  out  of  the  nuclein  of  the 


IMMUNITY.  391 

leucocytes,  together  with  reduction  of  the  alka- 
linity of  the  tissue  fluid,  goes  on  in  the  body 
itself,  basic  bodies  accumulate  and  act  as  auto- 
toxins,  and  the  leucocytosis  becomes  of  an  in- 
jurious character,  e.  g.  post-hsemorrhagic,  ca- 
chectic or  ante-mortem.  Hildebrandt  rendered 
rabbits  immune  against  the  ferment  emulsin, 
and  these  animals  then  showed  immunity  like- 
wise against  the  bacteria  of  rabbit-septicaemia. 
A  sort  of  natural  immunity  existed  normally 
and  this  was  heightened  by  a  special  impulse 
which  simulated  a  specific  protective  inocula- 
tion. In  all  these  cases  other  "  active  "  proteid 
bodies  acted  as  a  stimulus  upon  the  body  cells 
in  just  the  way  that  "  active  "  bacterial  proto- 
plasm is  supposed  to  do.  Natural  immunity 
is  thus  united  by  a  series  of  intermediate  links 
with  acquired  and  specific  immunity.  The 
common  feature  lies  in  the  stimulation  of  the 
particular  cell  territories  and  wandering  cells 
which  are  necessary  for  defence. 

Not  even  bodies  of  the  kind  under  consider- 
ation, however,  are  essential.  Ordinary  chem- 
ical substances,  if  they  are  able  to  interfere  in 
the  continuity  of  energy,  act  in  a  similar  way. 
This  is  indubitably  true  of  those  cases  in  which 
the  cure  depends  upon  the  excitation  of  inflam- 
mation, and  Liebreich  has  done  us  the  great 
service  of  showing  that  in  tuberculosis  the 


3Q2  BACTERIOLOGY. 

same  effect  can  be  brought  about  with  canthari- 
dates  as  with  tuberculin.1  Dixon  showed  sub- 
sequently that  creatin  had  a  similar  effect, 
Hebra  did  the  same  thing  for  thiosinaniin,  and 
Mosetig  for  teukrin,  and  Spiegler  has  still 
further  added  to  the  list  of  such  substances. 
To  the  same  class  of  therapeutic  methods  be- 
longs also  the  intravenous  injection  of  cinnamic 
acid  in  human  tuberculosis  (Landerer).  This 
substance,  likewise,  seems  to  act  through  the 
excitation  of  inflammation  and  so  far  has  ap- 
peared to  afford  the  best  results  obtained  with 
any  of  these  compounds. 

Localized  hypersemia,  such  as  makes  its 
appearance  in  consequence  of  the  diminution 
of  the  original  pressure  caused  by  opening 
the  peritoneum  may  act  favorably ;  and  cure 
has  in  fact  been  effected  in  peritoneal  tuber- 
culosis by  means  of  laparotomy.  Acting  on 
this  conception  Bier  has  recommended  pro- 
ducing artificial  hyperaemia  by  the  use  of 
bandages  in  cases  of  tuberculosis  of  the  limbs. 
We  must  assign  to  the  same  class  of  phenom- 
ena the  fact  that,  according  to  Rokitansky, 
tuberculosis  often  sets  in  when  an  anaemic 
condition  of  the  lungs  prevails  as  the  result  of 

1  Outside  of  the  determination  of  this  fact  little  consideration  has 
been  devoted  to  the  question  whether  these  salts  contribute  as 
much  as  or  more  than  tuberculin  to  the  cure  of  tuberculosis  in  man. 


IMMUNITY.  393 

defective  heart  action,  while  on  the  other  hand 
when  the  lungs  are  hypersemic  tuberculosis 
does  not  occur.  According  to  many  statements 
success  has  been  attained  by  the  use  of  small 
doses  of  quinine  and  arsenic  as  prophylactics 
against  malaria.  This  result  has  been  brought 
about  by  stimulating  the  body  cells,  so  as  to 
increase  the  defensive  powers  of  the  whole 
organism,  a  fact  that  for  the  sake  of  complete- 
ness I  have  mentioned  before  on  p.  162  in  con- 
nection with  the  discussion  concerning  the 
curative  effect  of  quinine. 

The  non-specific  actions,  however,  go  even 
further  than  this.  Rummo,  for  example,  has 
accustomed  white  mice  to  strychnine.  The 
serum  of  these  animals  contains  no  antitoxin ; 
they  have  not  acquired  immunity  against  snake 
venom  and  diphtheria,  but  they  have  acquired 
immunity  against  tetanus.  In  this  case  the 
modification  of  the  toxic  action  wrought 
through  the  stimulative  effect  of  the  strych- 
nine upon  the  spinal  cord  is  certain,  and  the 
influence  of  the  body  cells  is  strikingly  ap- 
parent. At  one  time  Behring  himself  pro- 
duced a  certain  degree  of  immunity  against 
anthrax  by  the  use  of  iodine  terchloride. 
Schutz  also  has  cured  with  iodine  terchloride 
animals  which  had  sickened  with  swine  ery- 
sipelas, and  has  protected  healthy  animals 


394  BACTERIOLOGY. 

against  the  disease  by  preventive  treatment. 
The  blood  of  animals  protected  with  iodine  ter- 
chloride  imparts  immunity  to  healthy  animals 
and  cures  animals  already  affected.  In  this 
case  the  notion  that  any  specific  antitoxins  are 
formed  is  entirely  without  justification ;  the 
action  may  depend  only  upon  some  general 
protective  power  that  is  acquired,  or  upon  a 
quantitative  intensification  of  the  defensive 
power  already  existing,  that  is,  upon  the  ren- 
dering active  of  the  cells  and  the  active  pro- 
teids  of  the  body  fluids. 

Although  many  negative  experiments  with 
other  bacteria  have  been  made,  yet  the  positive 
results  already  obtained  are  sufficient  to  make 
clear  the  falsity  of  the  ordinary  one-sided  in- 
terpretation of  "  specific"  protective  inocula- 
tion and  habituation  to  poison. 

General  metabolic  influences  also  may  simu- 
late specific  immunization.  Von  Fodor  has 
shown  that  the  resistant  power  of  rabbits  to 
anthrax  infection  is  increased  by  the  subcu- 
taneous addition  of  alkalies  to  the  blood  and 
Kurt  Miiller  has  shown  that  the  resistant 
power  of  white  rats  to  anthrax  is  exalted  by 
the  subcutaneous  injection  of  meat  extract. 
We  may  hence  justifiably  infer  that  it  is  pos- 
sible by  suitable  nourishment  together  with  a 
flushing  of  the  body  by  bodily  exercise  to 


IMMUNITY.  395 

heighten  the  general  immunity,  as  indeed  Pet- 
tenkofer  and  G.  Jager  have  demonstrated.  A 
properly  nourished  and  exercised  body  is  able 
to  cope  with  many  species  of  bacteria  simply 
by  means  of  its  normal  body  cells  and  fluids, 
without  its  being  necessary  for  us  to  assume 
the  existence  of  anything  heterogeneous  and 
"  specific  ". 

It  is  demonstrable,  therefore,  in  ways  that 
differ  quantitatively  according  to  the  method 
used,  that  by  means  of  very  various  impulses 
the  natural  protective  and  defensive  forces  of 
the  human  organism,  of  its  organs,  tissues, 
cells  and  fluids  can  be  made  active  or  by  stimu- 
lation raised  above  the  normal.  The  liberat- 
ing stimulus  then  becomes,  as  it  were,  a  stimu- 
lus to  increase  resistance.  It  may  even  be 
that  stimuli  of  entirely  different  characters 
evoke  a  defensive  reaction  as  great  as  was 
formerly  attributed  only  to  specific  stimuli, 
whereas  the  latter  stimuli  sometimes  bring 
about  only  a  tolerably  moderate  defensive  re- 
action. In  general,  however,  the  defensive  re- 
action which  is  provoked  by  isopathic  or 
specific  stimuli  is  the  stronger  and  more  per- 
sistent and  hence  often  appears  to  be  peculiar 
in  kind.  But  we  can  really  understand  every- 
thing that  the  mysterious  doctrine  of  specifi- 
city has  tried  zealously  to  render  obscure  by  re- 


396  BACTERIOLOGY. 

ference  to  what  is  already  known  of  the  physio- 
logical protective  forces  of  the  body  and  the 
manner  in  which  they  are  stimulated  or  called 
into  activity.  The  specific  methods  of  calling 
the  bodily  forces  into  activity  are  usually  to  be 
preferred,  since  stimuli  of  this  character  bear 
a  recognized  relation  to  the  defensive  organs 
of  the  body,  but  by  this  I  do  not  mean  to  claim 
that  they  are  the  sole  or  always  the  best  means 
of  producing  the  desired  effect.  Any  such 
notion  as  the  doctrine  of  specificity  must  be 
set  aside  if  we  do  not  wish  to  bar  the  road  to  a 
scientific  interpretation  of  immunity.  A  pro- 
tective inoculation  may  appear  specific  not 
only  when  it  is  brought  about  by  isopathic  or 
specific  bacteria  and  their  products,  but  also 
when  it  is  attained  by  means  of  stimuli  of  a 
wholly  different  kind.  On  the  other  hand  the 
use  of  appropriate  specific  stimuli  may  call 
into  activity  only  defensive  contrivances  of  a 
slight  and  generalized  character. 

The  question  is  not  whether  something  is 
demonstrated  or  demonstrable  in  every  case,  or 
whether  it  is  the  best  or  most  practical  thing, 
but  it  is  rather  whether  the  thing  exists  at  all. 
We  are  able  to  trace  back  the  various  forms  of 
specific  habituation  to  poison  and  protective  in- 
oculation, like  those  of  natural  curative  and  pro- 
tective power,  to  the  same  general  natural  law 


IMMUNITY.  397 

under  which  come  the  phenomena  of  natural 
immunity  and  predisposition  to  disease.  The 
possibility  of  recognizing  such  a  high  conform- 
ity to  law  in  these  broad  processes  seems  to  me 
to  impart  a  truer  perception  of  these  things  than 
the  totally  blind  and  mystical  idea  of  "  speci- 
fic "  activity,  a  conception  which  is  no  longer 
consistent  with  belief  in  organic  continuity. 
I  once  compared  such  boundaries  in  nature  to 
the  jurist's  treatment  of  his  paragraphs,  as 
projections  of  the  beams  in  our  eyes  which  we 
all  carry  on  account  of  the  limits  of  our  sub- 
jective knowledge.  Every  line  which  we  are 
able  to  obliterate  affords  us  truer  insight.  On 
the  other  hand  I  must  oppose  that  affected 
simplicit}^  which  is  not  the  mark  of  truth, 
however  it  simulates  it,  and  which  is  able  to 
see  in  bacteria  alone  the  cause,  the  prevention 
and  the  cure  of  infectious  disease.  It  is  not  a 
question  of  a  simple  equation  with  one  un- 
known quantity,  but  more  correctly  of  a  greatly 
involved  equation  with  three  variable  quanti- 
ties. 


CHAPTER  VII. 

THE   PREVENTION  OF  INFECTIOUS    DISEASE    BY 
COMBATING  THE  CAUSE  OF   THE    DISEASE. 

WHEN  the  devastating  disease  of  cholera  first 
invaded  Europe  early  in  the  present  century 
it  caused  great  mortality.  This  destruction  of 
life  led  the  authorities  first  in  England  and 
later  in  France  and  Germany,  to  make  accurate 
record  of  the  morbidity  and  mortality  statistics 
of  infectious  diseases,  both  independently  and 
in  their  relations  to  other  diseases.  The  re- 
form of  medical  statistics  begun  in  England 
at  this  time  afforded  science  its  first  basis  for 
the  comparison  of  the  data  of  disease. 

Epidemiological  observations  upon  cholera 
made  it  probable  that  cholera  is  not  strictly  a 
contagious  disease  but  that  it  sustains  rela- 
tions with  the  outside  world,  especially  with 
the  water  and  the  soil.  From  this  fact  im- 
partial observers  deduced  the  probability  that 
the  frightful  havoc  wrought  by  cholera  might 
be  due  to  the  unhygienic  surroundings  of  city 
dwellings  which  at  that  time  were  thoroughly 

bad,  and  they  declared  that  all  human   sur- 

398 


THE    PREVENTION   OF   INFECTIOUS   DISEASE.    399 

roundings  must  be  made  sanitary  and  whole- 
some. Under  the  pressure  of  events,  which  gave 
to  cholera  the  titleof  "  the  police  force  of  nature," 
not  only  a  complete  and  thorough  organization 
of  the  English  public  health  service  was  effect- 
ed, but  those  sanitary  reforms  in  sewerage 
and  water-supply  that  were  then  thought  to  be 
necessary,  were  introduced  upon  a  larger  scale 
and  the  carrying  out  of  such  measures  was 
often  made  compulsory.  The  result  justi- 
fied the  endeavors,  and  when  cholera  broke 
out  anew  its  violence  was  greatly  diminished 
and  it  was  altogether  suppressed  in  those  locali- 
ties where  sanitary  measures  of  this  sort  had 
been  adopted.  The  favorable  effect  of  these  re- 
forms was  shown  not  merely  in  the  case  of  in- 
fectious diseases  of  the  character  of  cholera  and 
typhoid  fever.  We  soon  learned  to  regard 
those  infectious  diseases  which  furnished  the 
larger  part  of  all  cases  of  sickness  and  death  as 
"  preventable  "  diseases.  Simon,  Parr,  Parkes, 
Pettenkofer,  and  Stamm  were  the  men  who 
were  foremost  in  furthering  this  work.  But 
in  spite  of  the  great  improvement,  all  diseases 
were  not  prevented.  The  influence  of  sanitary 
measures  made  itself  felt  chiefly  in  respect  to 
those  infectious  diseases  which,  from  their 
method  of  dissemination,  required  us  to  assume 
their  connection  with  the  outside  world,  while 


400  BACTERIOLOGY. 

the  effect  upon  the  so-called  constitutional  dis- 
eases like  tuberculosis, — which  we  must  now 
regard  also  as  an  infectious  disease — was 
less  marked  and  the  real  contagious  diseases 
like  small-pox  and  scarlet-fever  were  only  in- 
directly affected. 

If  we  bear  in  mind  what  was  remarked  ear- 
lier regarding  the  development  of  strict  para- 
sitism out  of  occasional  parasitism  (p.  257) 
and  that  of  this  latter  condition  out  of  simple 
putrefactive  power,  we  are  at  once  in  a  position 
to  understand  how  it  is  that  works  of  sanitation 
which  directly  improve  the  soil  and  water  may 
affect  directly  only  those  disease  germs  which 
stand  in  some  sort  of  relation  to  the  outer 
world.  Measures  of  this  kind  cannot  in  general 
act  directly  upon  the  occasional  saprophytes, 
and  the  strict  parasites  of  the  kind  found  in 
tuberculosis  and  relapsing  fever,  and  which 
may  possibly  be  present  in  the  acute  exanthe- 
mata like  typhus,  small-pox  and  scarlet  fever. 
When  such  measures  do  exert  an  ameliorat- 
ing effect  upon  these  diseases  and  diminish 
the  number  of  cases,  only  an  indirect  action 
can  be  claimed.  This  indirect  action  may  be 
exerted  in  different  ways.  These  measures 
may  for  example  hinder  or  prevent  the  passing 
over  or  transfer  of  disease  germs  to  human 
beings,  and  they  may  also,  through  the  im- 


THE   PREVENTION   OF   INFECTIOUS   DISEASE.   401 

provement  of  sanitary  conditions,  diminish  the 
predisposition  of  man  to  disease  and  increase 
his  power  of  resistance.  Hygienic  measures 
therefore  do  not  aim  necessarily  at  preserving 
every  life  at  all  cost,  but  rather  at  favorably 
modifying  the  constitution  of  man,  and  ele- 
vating the  general  hygienic  condition  of 
the  race.  Whereas  Pettenkofer  sees  in  the 
"  circumstances  of  time  and  place  "  and  their 
modification  by  works  of  sanitation,  an  in- 
fluence that  can  be  exerted  only  upon  the 
parasites  as  found  outside  of  the  body,  and 
Koch  considers  of  moment  only  the  influence 
of  these  measures  upon  the  transmission  of  the 
parasites,  it  was  proved  by  Hueppe  in  1887 
that  the  " local  disposition"  consists  also  and 
perhaps  chiefly  in  the  influence  of  the  local 
surroundings  upon  the  human  beings  living  in 
the  place.  We  may  now  hold  this  opinion 
also  on  the  basis  of  bacteriological  evidence. 
In  1889  Hueppe  and  Wood  discovered  that 
harmless  bacteria  found  in  a  certain  locality 
could  confer  protection  against  specific  dis- 
eases, while  on  the  other  hand  Metschnikoff 
discovered  in  1894  that  the  invasion  of  the 
cholera  bacteria  is  favored  by  the  presence  of 
certain  saprophytes.  Such  "  indigenous  ' 
saprophytic  microbes  may  act  upon  the  pre- 
disposition toward  disease  possessed  by  the 
26 


402  BACTERIOLOGY. 

dwellers  in  a  given  locality  so  as  either  to 
diminish  or  increase  it.  The  inhabitants  of 
any  locality  are  affected  not  merely  by  soil, 
water  and  air,  but  also  by  other  and  varying 
conditions  of  time  and  place,  for  example  by 
nourishment,  by  habitation  and  by  social 
environment,  as  we  see  exemplified  in  the  fact 
that  the  development  of  similar  industrial 
conditions  has  everywhere  brought  about  a 
parallel  increase  of  tuberculosis. 

The  so-called  works  of  sanitation  act,  then, 
by  influencing  favorably  certain  social  factors. 
But  this  influence  varies  greatly  according  to 
the  very  different  weight  which  the  predis- 
position to  disease,  and  the  conditions  for  the 
conveyance  of  the  disease  and  disease  germs 
possesses  in  the  various  infectious  diseases. 
Whatever  the  theory  of  the  matter  may  be, 
the  spirit  is  as  little  affected  by  our  interpre- 
tation as  is  the  spirit  of  the  law  by  craftily 
constructed  paragraphs.  I  must  hark  back 
again  to  the  multiplicity  of  the  phenomena 
involved  ;  in  this  chain  three  links,  to  keep  to 
my  comparison,  are  of  special  importance. 
One  of  them  has  been  viewed  by  Pettenkofer, 
and  another  by  Koch  in  a  one-sided  way,  but 
the  three  together  have  been  sufficiently  con- 
sidered by  no  one. 

If  we  remember  that  in  practice,  we  estimate 


THE    PREVENTION   OF   INFECTIOUS   DISEASE.   403 

provisionally,  though  not  quite  precisely,  the 
number  of  sick  persons  in  the  community  by 
the  actual  mortality,  then  the  total  mortality  can 
be  looked  upon  as  an  expression  of  the  force  of 
constitution  or  of  the  sum  of  the  bodily  energy 
of  the  inhabitants  of  a  town  or  country,  that 
is  convertible  into  effect  not  by  a  physio- 
logical but  by  a  pathological  stimulus.  The 
contrast  between  physiological  and  patholo- 
gical is  of  course  employed  only  in  an  an- 
thropocentric  sense  ;  for  nature  herself  deals 
only  with  a  struggle  for  existence,  with  a 
selection  of  the  fittest  to  resist  disease.  If  we 
remember  furthermore  that  all  forms  of  par- 
asitism can  develop  and  must  have  developed 
out  of  the  putrefactive  processes  so  essential 
in  the  cycle  of  life  phenomena,  we  are  at  once 
able  to  understand  how,  so  long  as  there 
exists  available  energy  in  a  form  departing 
from  that  of  the  normal  physiological  or- 
ganization, nature  will  cause  an  increase  in 
some  diseases,  a  decrease  in  others,  or  permit 
wholly  new  diseases  to  develop  out  of  the 
numberless  possibilities  which  putrefactive 
processes  hold  always  in  store. 

A  real  and  permanent  decrease  in  infec- 
tious disease  is  possible  only  when  there 
exists  less  energy  capable  of  release  .in  this 
form,  when  in  other  words  we  remove  the  pre- 


404  BACTERIOLOGY. 

disposition  to  disease  and  increase  the  resist- 
ance and  cause  thereby  all  setting  free  of 
energy  to  take  place  physiologically.  So 
long  as  this  is  not  the  case  infectious  diseases 
will  be  always  with  us,  though  some  of  those 
now  prevalent  may  disappear,  while  others 
will  remain,  and  entirely  new  ones  arise. 
Viewing  the  question  in  this  aspect,  it  is 
easily  seen  that  the  infectious  diseases  can  be 
designated  as  preventable  diseases  only  with 
some  reservation.  The  infectious  diseases 
are  the  expressions  of  an  actually  existing 
and  unavoidable  situation  or  state  of  adapta- 
tion, which,  however,  by  paying  heed  to  the 
causes  that  lead  to  it  may  to  a  certain  extent 
be  prevented  from  recurring  in  the  futiire. 
I  have  elsewhere  expressed  myself  in  a  similar 
way,  for  the  anthropocentric  conception  of 
disease  is  not  scientifically  tenable  and  is 
one  of  which  we  can  at  most  make  use  to  im- 
press public  functionaries  and  sanitary  police. 
Schleich  has  in  a  somewhat  different  way 
concisely  described  disease  as  "  a  form  of  the 
struggle  for  existence  against  those  injurious 
influences  to  which  man  is  not  yet  adapted. " 
The  process  of  adaptation  to  these  injurious 
influences,  however,  has  for  thousands  of  years 
been  decimating  the  human  race,  and  the 
nation  and  the  community  are  often  robbed 


THE    PREVENTION   OF   INFECTIOUS   DISEASE.   405 

of  their  most  worthy  members,  while  the  more 
worthless  individuals  prove  to  be  adapted  ;  in- 
fectious diseases  do  not  remove  with  certainty 
merely  the  anti-social  elements  of  the  com- 
munity, while  leaving  and  bringing  to  matu- 
rity only  the  socially  useful.  Hygiene  has 
accordingly  undertaken  the  task  of  removing 
these  injurious  influences.  This  reform  may 
be  brought  about  either  by  making  war  upon 
the  disease  germs,  or  by  combating  those  con- 
ditions of  life  which  are  of  importance  for  the 
disposition  either  of  man  or  of  the  parasites, 
or  which  have  an  influence  through  the  fact 
that  they  make  possible  the  transmission  of 
the  parasites  to  man. 

Measures  of  hygiene  bearing  directly  on 
the  cause  may  be  applied  to  different  links  of 
the  chain  to  prevent  its  closing,  that  is  to 
say,  to  prevent  the  outbreak  of  disease  in 
individuals  or  groups  of  individuals.  In  this 
method  of  contest  with  disease  many  more 
things  prove  useful  practically  than  might  be 
theoretically  supposed,  and  pure  reason  needs 
to  be  supplemented  by  practical  common 
sense.  Experience  has  certainly  a  word  to 
contribute.  Since  detailed  considerations  be- 
long to  the  more  restricted  province  of  hygiene, 
I  shall  simply  make  some  brief  statements,  for 
the  sake  of  completeness,  to  illustrate  the  in- 


406  BACTERIOLOGY. 

fluence  of  the  scientific  conception  of  bacteriol- 
ogy upon  the  improvement  of  individual  and 
national  health. 

The  removal  of  the  predisposition  to  disease 
is  the  most  thorough-going  way  of  making  all 
infectious  disease  impossible,  and  in  this 
direction  much  practical  advance  has  already 
been  made.  It  seems  to  me,  indeed,  that  in 
demanding  full  consideration  for  this  question, 
hygiene  carries  within  itself  a  powerful  edu- 
cative force  for  social  healthfulness,  the  signi- 
ficance of  which  for  the  future  hygiene  of  the 
race  can  perhaps  hardly  be  divined.  This 
force,  however,  can  make  itself  fully  felt  only 
through  the  medium  of  a  general  sanitary 
education.  In  the  preceding  century  and  in 
the  first  half  of  the  present  century,  J.  P. 
Frank,  Halle  and  Levy  attempted  to  bring 
this  about.  Men  were  to  be  observed  like 
hot-house  plants  and  only  the  hypochondriacs 
were  to  be  grown  large ;  they  were  to  eat  only 
-with  the  balance  and  control  the  amount  of 
their  drink  with  measuring  glasses, — in  the 
chemical,  not  in  the  Munich  sense, — they 
were  daily  to  ascertain  their  temperatures 
with  the  thermometer  in  order  that  no  mistake 
might  be  made.  Education  to  a  state  of  panic 
is  not  a  wholly  new  discovery  of  the  Kochian 
bacteriology,  and  the  earlier  products  of  the 


THE   PREVENTION   OF   INFECTIOUS   DISEASE.  407 

scare  system  are  certainly  just  as  ridiculous 
and  disgraceful  as  the  newest.  The  hygienists 
of  the  older  physiological  or  clinical  schools 
were  far  surpassed  in  hygienic  tact  by  true 
teachers  like  Basedow,  Rousseau,  Salzmann, 
Guts  Muths  and  Jahn,  and  among  these  we 
may  also  reckon  Frank,  who  maintained  that 
the  healthy  youth  must  be  kept  habitually  in 
good  condition  and  made  physically  hardy.  A 
true  hygienic  education,  for  the  attainment  of 
which  the  great  physicians  recommend  clean- 
liness, temperance  and  work,  can  never  lead 
to  effeminacy  and  fear  of  disease. 

This  is  not  the  place  to  enter  into  a  consider- 
ation of  details,  the  more  so  since  I  once  dis- 
cussed many  of  the  points  in  question  in  con- 
nection with  the  totally  neglected  hygienic  and 
national  aspect  of  the  woman  question.  In  our 
cities  much  mischief  is  generally  done  by  the 
notion  that  florid  children  are  healthy  chil- 
dren. The  florid  appearance  is  often  merely 
the  result  of  a  qualitative  overfeeding.  Espe- 
cially in  well-to-do  families  in  the  city,  chil- 
dren are  generally  nourished  with  a  diet  too 
rich  in  animal  proteid,  and  to  aid  the  digestion 
and  deglutition  of  this  food,  the  very  dangerous 
poison  alcohol  is  used  in  the  form  of  wine,  beer 
and  even  brandy.  But  even  where  conditions 
are  unusual  children  generally  cannot  help 


408  BACTERIOLOGY. 

drinking  too  much,  especially  when  eating, 
although  if  the  food  is  properly  prepared  no 
drink  is  usually  needed  while  eating,  and  chil- 
dren at  first  resist  instinctively  the  bad  ex- 
ample set  by  their  elders  in  this  matter.  The 
action  of  the  gastric  juice  and  the  other  diges- 
tive juices  is  impaired  by  much  drinking,  and 
the  specific  weight  of  the  body  is  diminished. 
An  over  concentrated  form  of  nourishment  on 
the  other  hand  causes  peculiar  chemical  bodies 
to  accumulate  in  large  quantities  in  the  intes- 
tine ;  these  are  taken  up  into  the  circulation 
and  act  injuriously  as  self-poisons  or  leuco- 
mains  and  as  substances  inducing  fatigue,  and 
at  times  may  even  bring  about  grave  manifes- 
tations of  disease,  such  for  example  as  are  rec- 
ognized in  tetany  and  coma.  Such  an  over- 
concentration  hinders  also  the  mechanical 
development  of  the  digestive  organs,  especially 
of  the  stomach,  so  that  the  adult  takes  as  small 
a  portion  of  food  as  a  child.  Many  ladies  af- 
ford astonishing  examples  of  this  condition, 
through  their  efforts  to  remain  slender  and 
interestingly  pale  by  taking  a  very  small  quan- 
tity of  food.  A  child  naturally  eats  a  large 
quantity  of  food  in  order  to  accustom  its  diges- 
tive organs  to  the  quantity  needed  later  by  the 
adult  and  to  properly  develop  the  capacity  of 
the  stomach,  and  an  increase  in  quality  and 


THE    PREVENTION   OF   INFECTIOUS   DISEASE.   409 

consequent  falling  off  in  quantity  works  little 
more  than  injury.  Coffee,  tea  and  alcohol  are 
no  drinks  for  children.  The  story  of  the 
youth  who  when  questioned  as  to  the  virtues 
of  the  old  Germans  declared  them  to  be  "  Treue, 
Wahrheitsliebe  uiid — Gastwirthschaft  "  is  in 
perfect  accord  with  the  present  customs  of  both 
children  and  adults.  Our  educated  youth,  in- 
stead of  fuddling  themselves  and  killing  time 
in  smoky  rooms  with  skat-playing,  would  do 
better  to  develop  themselves  in  mind  and  man- 
ners and  to  keep  the  body  strong  by  gymnas- 
tics, sports  and  athletic  games.  I  need  only 
mention  this  to  call  attention  to  a  common  error 
of  omission.  The  body  that  is  trained  and 
hardened  by  exercise  is  more  resistant  to 
disease  in  general,  as  Pettenkofer  and  G. 
Jager  have  shown.  The  flushing  out  of  the 
body  by  training,  with  the  consequent  increase 
in  its  specific  weight,  is,  as  G.  Jager  rightly  re- 
marks, an  important  method  of  obtaining  im- 
munity. To  the  same  end  a  proper  habituation 
to  the  feeling  of  thirst  is  very  important,  be- 
cause otherwise  this  feeling  leads  to  excess  in 
drinking,  and  to  drinking  at  the  wrong  times. 
The  regulation  of  diet  in  training  in  the  more 
limited  sense  should  never  be  carried  out  ac- 
cording to  a  fixed  scheme.  The  human  being 
does  not  possess  like  the  carnivora,  degenerate 


410  BACTERIOLOGY. 

sweat  glands,  and  consequently  large  and  sud- 
den losses  of  water  from  violent  exercise  have 
a  different  effect  upon  him,  and  the  kidneys 
are  thus  often  seriously  injured  through  igno- 
rance. Many  bacteriologists  taboo  raw  fruit 
and  salad,  and  this  precaution  may  be  wise, 
particularly  if,  as  Lahmann  recommends, 
qualitative  consideration  be  given  to  the  salts 
in  the  food,  specially  to  those  occurring  in 
green  vegetables.  I  have  found  that  in  train- 
ing very  remarkable  and  uniform  changes 
occur  in  the  relative  proportion  of  the  most 
important  salts  in  the  urine  as  compared  with 
the  proportion  appearing  in  a  condition  of  rest 
or  of  light  work ;  the  amounts  of  urea,  uric 
acid,  and  phosphoric  acid  are  affected  in  very 
different  ways,  a  condition  that  indicates  a  pro- 
found alteration  of  metabolism  and  must  surely 
exert  an  influence  upon  heart  and  kidneys  if 
proper  precautions  are  not  taken.  These  ex- 
treme degrees  of  metabolic  disturbance  are 
connected  with  the  ordinary  conditions  of  life 
through  all  possible  intermediate  stages.  The 
place  of  habitation  as  well  as  the  nourishment 
must  be  carefully  looked  after.  These  things 
may  all  be  learned  in  a  properly  directed  edu- 
cation just  as  easily  as  table  manners,  so  that 
they  become  as  it  were  instinctive.  There  is 
no  greater  folly  than  to  change  suddenly  an 


THE    PREVENTION   OF   INFECTIOUS   DISEASE.   4!  I 

accustomed  and  perfectly  suitable  method  of 
nourishment  because  of  fright  at  the  outbreak 
of  an  epidemic. 

In  contrast  to  presumably  unreasoning  ani- 
mals, the  human  being,  who  is  supposed  to  be 
capable  of  reasoning,  has  frequently,  strange 
to  say,  behaved  himself  most  foolishly  in  the 
matter  of  food  and  has  accentuated  this  fault 
by  his  lack  of  sense  in  the  matter  of  drink.  It 
is  everywhere  observed  that  the  misuse  of  al- 
cohol increases  the  danger  of  cholera  infection, 
and  if,  as  H.  Weyl  believes,  brewers  are  ex- 
empt from  this  rule  the  fact  may  well  be  due 
to  the  circumstance  that  people  of  this  class 
are  picked  for  their  vigor  and  are  large  eaters. 
Where  inordinate  abstemiousness  exists  as  the 
result  of  poverty,  the  trouble  may  be  remedied 
by  proper  interposition,  as  is  seen  for  example 
in  the  success  which  has  attended  the  feeding 
of  poor  school  children.  Hunger  is  a  power- 
ful aid  to  cholera,  and  it  may  well  be  supposed 
that  the  first  pandemic  of  cholera,  so  pregnant 
with  ill  for  the  future,  arose  from  the  circum- 
stance that  the  seemingly  insignificant  en- 
demic disease  happened  to  coincide  with  one 
of  those  great  famines  that  occur  in  India  from 
time  to  time. 

The  whimsical  misconceptions  about  such 
matters  which  usually  prevail  among  us  in 


412  BACTERIOLOGY. 

times  of  cholera  epidemics  have,  with  reference 
to  the  wretched  conditions  that  existed  during 
the  cholera  epidemic  at  Hamburg  in  1892, 
been  well  characterized  by  Else  Hueppe : 
"  Whoever  wished  to  eat,  drink  and  live 
strictly  according  to  the  way  prescribed  must 
almost  forego  the  habit  of  eating  and  drink- 
ing, must  change  his  whole  mode  of  life  with- 
out receiving  anything  better  in  exchange. 
This  necessarily  leads  to  the  greatest  absurdi- 
ties. Of  what  use  is  it  to  recommend  spring 
water  or  red  wine  to  a  man  when  he  has  only 
bad  brandy  with  bad  water?  The  thirsty 
man  drinks  even  out  of  a  pool !  What  is  a 
poor  devil  to  think  when  he  hears  of  investiga- 
tions upon  the  relations  of  the  comma  bacillus 
to  caviar  or  to  tropical  fruits  while  he  is  hardly 
able  to  obtain  a  piece  of  bread  or  a  potato  ?  " 

We  need  an  education  in  hygiene  which 
shall  not  inculcate  the  fear  of  disease ;  such 
an  education  is  both  an  individual  and  a 
social  question  and  sharp  separation  of  the 
two  is  simply  impossible.  As  with  the  in- 
dividual the  sins  of  the  father  are  visited 
even  upon  the  fourth  generation,  so  social 
ills  affect  the  innocent  together  with  the 
guilty.  The  minors,  individual  and  social, 
need  our  protection  against  commercial  ex- 
ploitation and  need  also  a  hygienic  protec- 


THE    PREVENTION   OF   INFECTIOUS   DISEASE.    413 

tion.  The  warfare  against  social  misery  means 
also  protection  to  trie  well-to-do  upon  a  side 
on  which  they  are  themselves  powerless.  It 
is  undoubtedly  possible,  by  the  bettering  of 
our  ways  of  life  and  by  the  hygienic  education 
of  the  community,  to  diminish  greatly  the  sum 
of  predisposition  to  disease  and  to  heighten 
the  immunity  of  the  whole  people.  Personal 
and  public  measures  of  sanitation,  thus  under- 
stood and  administered,  constitute  also  a  form 
of  racial  hygiene  deliberately  conscious  of  the 
end  to  be  secured.  The  actual  solidarity  of 
the  interests  of  all  classes  of  people  and  a 
knowledge  of  the  practical  limits  of  egotism 
will  gradually  bring  to  maturity  more  practi- 
cal social  hygiene  than  any  appeal  to  our 
sentiments  of  humanity. 

Among  individual  measures  of  this  charac- 
ter cleanliness  may  claim  an  altogether  special 
place,  that  cleanliness  which  the  Englishman 
says  is  health  itself,  and  which  I  have  declared 
to  be  the  first  and  better  half  of  disinfection. 
But  in  this  respect,  also,  education  must  lay  the 
foundation.  It  must  be  a  thing  taught  in  the 
common  schools,  in  the  factories  and  the  work- 
shops ;  in  the  army  it  has  already  achieved 
great  success.  I  think  that  Else  Hueppe 
grasped  the  kernel  of  the  matter  when  with 
reference  to  the  terrible  social  misery  which 


414  BACTERIOLOGY. 

the  Hamburg  cholera  epidemic  revealed,  she 
acknowledged  that  the  better  situated  individu- 
als were  raised  quite  by  themselves  above  the 
surrounding  uncleanliness  but  added  "  When, 
with  the  present  facilities  for  compassing 
cleanliness,  filth  continues  to  exist,  the  general 
conditions  of  life  must  be  at  fault  and  for  that 
reason,  in  such  an  unclean  locality,  there  is 
always  found  diminished  resistance  of  the  body 
toward  disease.  This  fact  helps  to  explain 
somewhat  more  adequately  than  any  one- 
sided consideration  of  disease  germs  and  con- 
tagion the  difference  in  resistant  power  which 
is  so  strikingly  to  the  disadvantage  of  the 
poor.  The  disease  germs  are  certainly  widely 
disseminated  in  any  epidemic,  and  some  door- 
way by  which  contagion  may  enter  is  to  be 
found  everywhere.  But  in  the  case  of  the 
well-to-do  the  main  avenues  of  entrance  are  for 
the  most  part  warded  better  than  among  poor 
people  because  the  whole  bodily  organization 
is  in  better  condition." 

In  this  education  to  healthfulness,  just  as 
in  Brehmer's  method  for  the  cure  of  tubercu- 
losis, no  regard  at  all  is  taken  of  the  disease 
germ  ;  the  predisposition  of  the  man  alone  is 
kept  in  view  and  this  predisposition  is  acted 
upon  by  means  of  those  general  conditions  of 
life  of  which  I  have  made  mention  earlier,  so 


THE   PREVENTION   OF   INFECTIOUS   DISEASE.   415 

that  the  intentional  modification  of  these  con- 
ditions of  life  may  affect  the  predisposition 
toward  disease.  The  microbes  that  are  present 
in  any  given  locality  may  be  able,  as  already 
pointed  ont,  to  act  in  such  a  way  as  either  to 
heighten  or  diminish  the  predisposition  to  dis- 
ease, so  that  in  this  respect  also  the  influence 
exerted  upon  the  body  may  possibly  be,  and  in 
individual  cases  can  even  be  demonstrated  to 
be,  a  particular  example  of  the  action  of  exter- 
nal conditions. 

Along  this  line  of  hygienic  education,  in  ad- 
dition to  a  comprehensive  supervision  of  bodily 
welfare  in  the  schools  through  gymnastics, 
athletic  sports  and  games,  the  controlling 
authorities  should  see  to  the  creation  and  ad- 
vancement of  a  system  of  instruction  in  scien- 
tific and  practical  hygiene  adapted  to  the  capac- 
ity of  the  schoolchildren.  There  should  be,  in 
connection  with  the  instruction  in  natural  his- 
tory and  natural  science,  instruction  in  hygiene 
planned  respectively  for  the  common  schools, 
the  secondary  schools  and  the  professional 
schools.  Starting  from  the  structure  and 
mechanism  of  the  human  body  and  the  pre- 
sentation of  its  daily  needs  it  is  possible  to  ar- 
rive at  some  understanding  of  the  general  con- 
ditions of  life  and  so  advance  from  personal 
hygiene  to  public  hygiene.  Along  this  same 


416  BACTERIOLOGY. 

road  the  practical  importance  of  self  help  in 
cases  of  misfortune  might  be  taught.  And  in 
the  Hochschulen  and  the  Seminars,  technolo- 
gists, administrative  officers  and  teachers 
should  find  opportunity  for  familiarizing  them- 
selves with  the  facts  of  hygiene,  each  according 
to  his  special  needs,  in  order  that  he  may  be 
able  to  conduct  his  work  in  the  real  service 
of  the  people.  In  this  important  matter  of 
hygienic  instruction  Germany  and  Austria 
are  extraordinarily  backward,  and  are  far  out- 
stripped by  some  countries,  as  for  example  by 
Hungary. 

Besides  the  general  increase  of  the  power 
of  resistance,  that  is  rendered  possible  through 
the  use  of  the  measures  I  have  suggested, 
it  is  possible  to  gain  an  isop'athic  or  spe- 
cific resistance  against  certain  diseases  by 
means  of  preventive  vaccination.  I  may  re- 
fer my  readers  to  the  thorough  treatment  of 
this  topic  in  the  preceding  chapter  (p.  314) 
and  content  myself  here  with  a  statement 
of  the  fact  that  the  old  method  of  vaccination 
against  small-pox  by  means  of  cow-pox  has, 
with  but  slight  modifications,  stood  the  test 
of  time.  Even  the  opponents  of  vaccination 
now  direct  their  attacks  rather  against  com- 
pulsory vaccination  than  against  the  inocula- 
tion itself,  so  far  at  least  as  they  are  candid 


THE   PREVENTION   OF  INFECTIOUS   DISEASE.   417 

and  equipped  with  the  necessary  rudiments  of 
knowledge.  I  cannot,  however,  touch  here 
upon  the  question  in  detail  and  shall  simply 
content  myself  with  reiterating  the  statement 
that  those  countries  possessed  of  a  system  of 
compulsory  vaccination,  that  is  to  say,  of  an 
effectual  protective  inoculation,  make  such  an 
extraordinarily  favorable  showing  that  the  op- 
posite condition  that  exists  in  other  countries 
constitutes  the  very  best  refutation  of  the  op- 
ponents of  vaccination.  In  Germany,  since 
the  introduction  of  compulsory  vaccination, 
not  as  many  as  one  in  100,000  living  inhabit- 
ants has  died  of  the  small-pox,  while  the  mor- 
tality in  Austria  is  about  60  and  in  Hungary 
about  450  times  as  great.  In  Saxon}7,  between 
1886-1892,  71  persons  died  of  small-pox;  in 
Bohemia,  19,607. 

The  more  recent  work  upon  protective  in- 
oculation has  developed  no  practical  result  for 
man.  But  the  work  has  not  been  wholly 
without  practical  result,  since  protective  inoc- 
ulation of  cattle  against  symptomatic  anthrax 
may  be  set  down  as  completely  successful,  and 
the  protective  inoculations  against  anthrax  and 
swine  erysipelas  have  at  least  been  of  benefit 
to  certain  districts. 

Far  more  successful  up  to  the  present  has 

been  the  struggle  against  external  conditions 

27 


41 8  BACTERIOLOGY. 

that  favor  disease,  and  in  part  also  that  against 
the  faulty  social  conditions  that  operate  to  this 
end.  It  is  primarily  due  to  the  adoption  of 
such  measures  that  civilized  states  are  not  now 
seriously  threatened  by  diseases  like  cholera. 
The  betterment  of  the  subsoil  by  drainage 
or  canalization,  and  the  various  modes  of  re- 
moval or  destruction  of  the  waste  products  of 
human  life  and  habitation  have  increased  the 
healthfulness  of  our  dwellings  and  improved 
the  quality  of  that  indoor  climate  to  which  city 
dwellers  are  inevitably  exposed  much  of  the 
time.  Those  substances  whose  soluble  or  gas- 
eous decomposition  products  are  offensive  and 
diminish  our  capacity  for  resistance  to  disease 
are  removed  from  our  vicinity.  The  intro- 
duction into  the  animal  body  of  soluble  pro- 
ducts of  putrefaction  at  the  same  time  with 
infective  material  favors  infection  even  in  ex- 
periments upon  animals  ;  with  such  assistance 
germs  less  virulent  than  the  normal  are  able 
to  bring  about  infection,  and  attenuated  germs 
become  again  infective.  Attempts  to  prove  by 
animal  experiments  that  the  gaseous  products 
of  putrefaction  have  a  similar  effect  have  not 
wholly  succeeded.  But  there  is  this  to  be  re- 
membered, namely,  that  the  animals  used  in  our 
experiments  are  accustomed  to  a  very  different 
atmosphere  from  that  which  we  ourselves 


THE    PREVENTION    OF   INFECTIOUS   DISEASE.   419 

breathe.  Dogs  and  rats  are  in  part  carrion  feed- 
ers ;  rabbits,  guinea-pigs,  rats  and  mice  live 
crowded  in  narrow  burrows  or  holes  in  which 
such  a  stench  prevails  as  would  nauseate  a  hu- 
man being.  To  conclude  from  negative  experi- 
ments that  gaseous  decomposition  products 
have  no  influence  in  diminishing  man's  resist- 
ance to  disease  would  be  a  gross  laboratory  fal- 
lacy. The  man  who  is  accustomed  to  pure  air 
does  in  fact  become  ill  in  the  bad  air  of  the  de- 
fectively aerated,  overcrowded  and  insufficiently 
lighted  dwelling  of  the  proletarian.  The  in- 
stinct for  cleanliness  is  fostered  by  such  hy- 
gienic measures  as  can  be  directed  to  over- 
coming these  improper  conditions  and  the  pure 
air  itself  affects  favorably  the  respiratory  or- 
gans and  occasions  deep  breaths  to  be  taken. 
The  practical  application  of  these  facts  together 
with,  above  all,  the  introduction  of  pure  water 
has  gradually  changed  into  almost  universal 
cleanliness,  the  uncleanliness  that  was  once 
prevalent  in  continental  Europe,  and  that  had 
crept  in  since  the  Thirty  Years'  War.  A  sup- 
ply of  good  water  free  from  all  suspicion  of 
infection,  removes  any  direct  relations  which 
might  otherwise  exist  between  ourselves  and 
the  infiltrated  subsoil  ;  on  the  other  hand  a 
bad  well  in  the  neighborhood  might  bring 
us  into  direct  contact  with  contaminated  soil. 


420  BACTERIOLOGY. 

Virchow  long  ago  attributed  the  immunity  to 
cholera  shown  by  the  city  of  Wiirzburg  to  the 
fact  that  a  good  water  supply  had  put  an  end 
to  the  relations  with  the  filth-saturated  earth. 
Dwellings  supplied  with  abundant  natural 
light  and  with  pure  air  must  gradually  aug- 
ment this  advantage. 

The  foundation  for  these  reforms  must  still 
frequently  be  laid  by  an  improvement  of 
the  building  laws  and  by  energetic  measures 
against  dishonest  contractors.  Care  for  the 
welfare  of  the  people  has  already  made  pro- 
gress in  Germany.  Cities  that  neglect  their 
duty  must,  as  in  England,  be  legally  com- 
pelled to  it.  Unfortunately  these  very  hy- 
gienic questions  generally  receive  shamefully 
inadequate  consideration  in  representative  as- 
semblies. Often  they  are  employed  for  catch- 
ing votes  before  the  election  and  afterwards 
with  affecting  unanimity  are  forgotten  by  all 
parties.  Matters  of  this  kind,  in  which  all 
classes  are  concerned  in  an  equal  degree,  are 
not  well  adapted  for  placing  one's  favorite  party 
in  a  superior  position,  hence  the  subject  is 
dropped  altogether.  Unfortunately  many  phy- 
sicians have  shown  themselves  even  more  back- 
ward in  such  matters  than  the  administrative 
officers.  And  yet  there  is  hardly  anything 
more  full  of  import  for  the  people  at  large  than 


THE    PREVENTION   OF   INFECTIOUS   DISEASE.   421 

the  national  health,  for  physical  well-being  af- 
fords the  indispensable  basis  for  all  efforts  of  a 
social  and  national  kind.  No  civilized  conti- 
nental state  yet  possesses  a  central  official  board 
of  health,  and  we  have  not  yet  obtained  very 
much  benefit  from  the  advisory  boards  which  do 
more  for  the  decoration  and  glorification  of  the 
administration  than  in  really  safeguarding  the 
national  health.  When  by  the  aid  of  hygiene 
the  efforts  of  physicians  have  reached  their 
culmination,  and  prevention  of  disease  is  rec- 
ognized as  better  than  cure,  then  in  the  spirit 
of  our  modern  striving  after  the  social  ideal  we 
must  turn  also  to  the  urgent  task  of  reforming 
our  Health  Departments  in  accord  with  the 
theory  and  practice  of  public  hygiene.  The 
hygiene  of  the  community  afforded  us  our  first 
and  most  useful  social  institutions  ;  in  this 
field  has  been  proved  the  possibility  of  accom- 
plishing great  social  undertakings,  and,  in 
contrast  to  the  almost  exclusively  bureaucratic 
treatment  of  social  questions  in  parliament, 
we  have  here  made  substantial  gains.  None 
the  less,  hygiene  has  not  yet  obtained  the 
place  belonging  to  it  in  sanitary  administration. 
The  latter,  instead  of  being  always  prepared  to 
act  in  the  spirit  of  preventive  hygiene,  for  the 
most  part  plods  on  in  the  good  old  way  with 
"  fresh  emendations  to  the  appendix  of  the 


422  BACTERIOLOGY. 

modified  supplement  of  the  most  recent  pro- 
visional administrative  instructions." 

While  the  conditions  predisposing  to  disease 
which  are  met  with  in  faulty  social  conditions 
and  in  the  general  substrata  of  life,  such 
as  air,  water,  soil  and  food,  act  chiefly 
'upon  the  human  susceptibility  to  disease,  and 
the  improvements  made  in  these  particulars 
diminish  this  susceptibility,  they  act  in  part 
also  by  affecting  the  dissemination  of  the  dis- 
ease germs.  This  fact  was  known  long  before 
the  days  of  bacteriology  through  data  of  the 
weightiest  kind  furnished  by  epidemiology. 
In  all  these  matters,  however,  bacteriology  has 
made  us  more  certain  of  our  ground.  Form- 
erly we  could,  if  we  wished,  assume  with 
Pettenkofer  that  cholera  was  not  spread  by 
drinking-water,  and  could  quietly  omit  reform 
in  this  matter  from  the  order  of  the  day.  I 
maintained  in  1889,  with  the  unanimous  ap- 
proval of  the  German  association  of  water  tech- 
nologists and  of  the  international  congress  of 
hygiene  at  Vienna,  that  the  once  insoluble 
question  concerning  proof  of  infection  with 
drinking-water  after  the  outbreak  of  an  epi- 
demic is  now  a  superfluous  one,  and  that  we 
are  in  a  position  to  convince  ourselves  before- 
hand at  any  moment  whether  a  given  source 
of  water  makes  infection  at  all  possible.  We 


THE    PREVENTION    OF   INFECTIOUS   DISEASE.   423 

are  able  now  in  every  case  to  close  the  well 
before  the  child  has  fallen  in  ;  we  need  not  delay 
action  until  an  epidemic  makes  its  appearance. 
In  1892  Hamburg  was  scourged  with  cholera 
for  its  negligence  about  water-supply,  yet  that 
harmful  consequences  were  likely  to  flow  from 
this  neglect  had  long  been  predicted  by  all 
physicians  and  technologists  capable  of  judg- 
ing in  the  matter.  Applied  correctly  and  sen- 
sibly bacteriology  is  certainly  able  to  assist  our 
insight  into  such  questions  and  a  science  of 
hygiene  minus  bacteriology  is  simply  impossi- 
ble. In  our  estimation  of  external  conditions 
according  to  their  ability  to  spread  infectious 
disease,  bacteriology  has  afforded  great  service, 
and  our  former  inability  to  judge  of  these  rela- 
tions from  the  standpoint  of  the  possibility  or 
impossibility  of  infection  has  already  given  way 
to  a  true  advance  in  the  direction  of  a  prac- 
tical preventive  hygiene.  To  be  sure,  little 
legislative  attention  has  yet  been  paid  to 
this  point,  and  the  legal  regulation  of  the  water 
question  which  was  urged  by  me  at  the  inter- 
national congress  of  hygiene  in  Vienna  in 
1887  still  remains  unaccomplished  in  spite  of 
the  fact  that  I  brought  up  the  matter  anew  in 
London  in  1891  and  in  Budapesth  in  1894, 
and  again  proved  that  such  regulation  could 
be  enforced.  The  sentiment  that  attaches 


424  BACTERIOLOGY. 

value  to  the  sanitary  welfare  of  the  whole 
community  is  for  the  most  part  lacking  in  our 
government.  We  almost  always  refrain  from 
expending  at  the  right  time  some  thousands 
of  dollars,  and  then  when  an  epidemic  is  pre- 
cipitated in  our  midst  we  sacrifice  millions  in 
paralysis  of  commerce  and  manufactures,  as 
Hamburg  was  forced  to  do  in  1892. 

The  outlook  is  less  promising  in  the  matter 
of  the  immediate  conquest  of  the  disease  germs. 
The  Pasteur-Tyndall-Miquel  period  when  the 
air  was  supposed  to  contain  clouds  of  bacteria 
was  followed  by  the  Kochian  era  when  all  fluids 
were  declared  to  be  infected,  when  stationary 
and  transportable  cuspidores  were  devised, 
and  when  the  disinfection  nuisance  reached  an 
unprecedented  height.  In  this  latter  period 
an  imperial  decree  dealing  with  infectious 
disease  was  promulgated  in  the  form  of  a  law 
for  safeguarding  the  people  by  means  of  penal 
enactments  ;  to  execute  this  law  one  half  of  the 
people  of  Germany  would  have  to  be  changed 
into  guardians  of  the  other  half  to  preserve 
them  from  harm  or  to  watch  them  during  their 
imprisonment  for  misdemeanors — with  the  ex- 
ception of  the  children,  of  course,  who  already 
have  guardian  angels. 

The  general  works  of  sanitation,  whose  re- 
lations to  predisposition  to  disease  have  been 


THE   PREVENTION   OF   INFECTIOUS   DISEASE.    425 

already  set  forth,  may  prove  also  of  value 
through  their  action  upon  the  disease  germs. 
By  improvement  of  air,  water  and  soil  and  by 
control  of  the  food  supply  the  dissemination  of 
disease  germs  can  be  restricted  and  even  pre- 
vented. In  this  respect  bacteriology  has  often 
led  to  a  correction  of  the  practice  of  earlier 
times  and  has  especially  strengthened  in  es- 
sential points  the  simple  methods  of  pro- 
cedure in  vogue  in  England. 

Disease  germs  that  have  somehow  found 
their  way  to  the  deeper  layers  of  the  soil  may 
probably  maintain  their  vitality  for  years  since 
they  are  there  withdrawn  from  competition 
with  saprophytes,  and  the  absence  of  air  to- 
gether with  the  presence  of  moisture  favors  the 
continued  existence  of  the  germs  without  per- 
mitting their  multiplication.  In  this  way 
may  be  explained  the  fact  that,  according  to 
the  statement  of  Donitz,  cholera  at  one  time 
broke  out  in  Japan  among  soldiers  who  were 
reinterring  properly  the  bodies  of  their  fellows 
who  had  died  from  cholera  the  year  previously 
and  had  been  buried  in  a  common  grave. 
Similarly  cholera  broke  out  in  a  single  street 
in  a  small  city  of  Nassau  when  excavations 
were  going  on  in  the  street  the  year  after  a 
cholera  epidemic.  In  cases  of  this  kind  proper 
sanitary  measures  at  the  outset  would  have 


426  BACTERIOLOGY. 

prevented  subsequent  resurrection  of  the  dis- 
ease germs. 

Works  of  sanitation  have  also  the  effect  of 
interfering  with  the  foo$  requirements  of  dis- 
ease germs.  In  pure  soil  or  in  good  water  the 
disease  germs  either  cannot  multiply  on  ac- 
count of  the  competition  of  the  common  germs 
of  putrefaction,  or  else  they  adapt  themselves 
to  the  new  and  unfavorable  conditions  of  life 
and  suffer  loss  of  their  virulence  and  infective 
power  ;  that  is,  they  lose  their  ability  to  attach 
themselves  to  man,  to  multiply  and  to  form 
poisons  and  they  finally  become  again  simple 
saprophytes.  Until  recently  comma  bacilli  in 
water  were  always  sought  for  in  vain,  but  after 
the  cholera  outbreak  of  1892  and  1893  the  ba- 
cilli were  found  in  many  places  and  were  often 
present  in  abundance  in  the  rivers  Elbe,  Spree, 
and  Seine.  These  comma  bacilli  possessed 
characteristics  of  such  a  kind  as  to  cause  them 
to  be  naturally  regarded  as  cholera  bacilli 
jnodified  and  rendered  more  saprophytic  by  an 
aquatic  existence.  It  is  to  be  borne  in  mind 
in  this  connection,  to  be  sure,  that  individual 
germs  may  escape  this  process  of  adaptation ; 
but  the  purer  the  soil  or  the  water,  the  less 
does  any  such  conserving  influence  come  into 
play  and  the  greater  are  the  chances  that  the 
disease  germs  will  succumb  in  one  way  or 


THE   PREVENTION   OF   INFECTIOUS   DISEASE.  427 

another.  Virulent  germs  may  persist  longest 
in  the  slime  at  the  bottom  of  lakes  and  rivers 
because  in  such  places  abundant  food  ma- 
terial exists  together  with  restriction  of  the 
air  supply. 

The  competition  with  the  bacteria  of  putre- 
faction to  which  disease  germs  are  subjected  acts 
in  such  a  way  that  even  in  cesspools  and  dung- 
heaps  disease  germs  perish  as  a  rule,  so  that 
practically  the  disinfection  of  such  localities  is 
to  say  the  least  needless.  It  only  exception- 
ally happens  that  the  emptying  of  a  cesspool  is 
followed  by  an  outbreak  of  typhoid  fever.  Such 
a  proceeding  as  the  application  of  milk  of  lime 
to  manure  heaps  affects  sensible  people  merely 
by  exciting  their  sense  of  the  ridiculous. 

Works  of  sanitation  are  effectual  also  in  a 
more  indirect  way.  The  human  being  who 
has  become  immune  through  their  agency  may 
himself  have  such  an  influence  upon  the  in- 
vading parasite  that  the  virulence  of  the  latter 
becomes  diminished.  The  virulence  of  disease 
producing  bacteria  maintains  its  force  or  may 
even  be  increased  in  susceptible  animals,  but 
generally  decreases  and  may  disappear  in  the 
process  of  adaptation  to  resistant  or  immune 
animals,  a  fact  that  was  first  established  by 
Pasteur  (cf.  p.  175). 

Works  of  sanitation  act  upon  saprophytes 


428  BACTERIOLOGY. 

as  well  and  interfere  with  the  dangerous  forms 
of  proteid  putrefaction  which  play  a  role  in 
intoxications  and  are  of  importance  in  the  on- 
togeny and  phylogeny  of  parasites,  and  they 
do  good  service  also  by  favoring  beneficial 
forms  of  decomposition  and  oxidation,  such 
for  instance  as  the  process  of  nitrification  or 
formation  of  saltpeter  in  the  soil.  In  this  way 
also  they  diminish  the  possibility  of  an  adapta- 
tion of  saprophytes  to  parasitic  conditions  of 
existence ;  they  diminish,  that  is,  the  likelihood 
of  the  origination  of  new  infectious  diseases. 
There  is  hence  no  question  that  works  of  san- 
itation do  exert  an  influence  upon  the  disease 
germs,  although  this  influence  has  not  the  high 
importance  which  we  must  attribute  to  their 
effect  upon  human  predisposition  toward  dis- 
ease. 

Human  beings  may  still  be  counted,  and,  as 
individuals  or  groups  of  individuals,  are  amen- 
able to  treatment,  but  such  is  not  the  case  with 
the  milliards  of  disease-germs.  An  attempt  to 
overcome  the  plague  of  flies  by  killing  the  in- 
dividual flies  would  justly  be  laughed  at,  and 
yet  there  have  not  been  wanting  bacteriologists 
who  a  la  Zacherl  would  take  arms  against  the 
individual  bacteria  and  try  to  fell  to  the  ground 
every  single  bacillus. 

In  localities  where  the  danger  from  fire  is 


THE   PREVENTION   OF   INFECTIOUS   DISEASE.   429 

slight  we  may  build  our  houses  of  wood  and 
thatch  them  with  straw.  Where,  however,  the 
danger  is  greater  we  must  build  our  houses 
fireproof  in  order  that  when  one  house  takes 
fire  a  whole  district  shall  not  burst  into  flames. 
Compared  with  the  quality  of  material  the 
measure  of  extinguishing  the  separate  sparks 
is  of  less  importance  in  preventing  the  spread 
of  the  conflagration.  The  method  of  spark 
chasing  does  not  help  much  in  the  case  of 
buildings  of  wood  and  straw,  as  can  be  seen  in 
out-of-the-way  villages,  or  even  in  Scandinavian 
cities  which  are  still  built  wholly  of  wood. 
The  satisfaction  of  afterwards  seeing  the  in- 
cendiary caught  and  punished  helps  no  one  to 
regain  his  property.  The  extinction  of  sparks 
will  always  be  less  valuable  service  to  the  civ- 
ilized community  than  the  intelligent  construc- 
tion of  the  house  and  the  adaptation  of  it  to 
existing  conditions. 

The  combating  of  infectious  diseases  by  war- 
ring directly  with  the  disease  germs,  the  so- 
called  method  of  disinfection,  must  be  kept 
within  reasonable  limits  and  employed  only 
where  we  are  able  to  assume  that  disease  germs 
really  exist. 

It  may  facilitate  our  understanding  of  this 
simple  demand, — which  I  advanced  in  1889  *n 
opposition  to  the  standpoint  of  Koch,  at  that 


430  BACTERIOLOGY. 

time  extreme, — if  I  remind  my  readers  that  the 
antiseptic  method  of  treating  wounds,  devised 
by  the  genius  of  Lister  and  aimed  directly  at 
the  germs  present  in  the  air  and  alighting 
upon  wounded  surfaces,  is  carried  out  to-day 
only  in  a  rather  small  number  of  cases.  Op- 
erative medicine,  taking  up  again  a  method 
introduced  by  Semmelweiss  in  1847  an(^  im~ 
proved  in  accordance  with  the  spirit  of  the 
times,  now  generally  prefers  to  proceed  asep- 
tically  from  the  outset,  and  to  rely,  and  with 
greater  success  than  by  the  other  method,  upon 
the  natural  aids  man  possesses  against  his 
small  foes. 

My  conception  of  disinfection  is  similar  to 
this.  I  would  use  methods  of  disinfection  only 
for  the  purpose  of  preventing  disease.  What 
disinfection  cannot  accomplish  in  this  way  it 
cannot  accomplish  at  all,  as  we  ought  to  have 
learned  by  this  time.  Whoever  expects  more 
of  disinfection  than  this  deceives  himself  and 
others,  and  leads  to  an  ill-advised  expenditure 
of  money  which  might  be  better  employed  in 
effective  works  of  sanitation. 

But  even  where  it  is  really  possible  to  dis- 
infect with  an  appearance  of  success,  disinfec- 
tion does  not  accomplish  anything  save  where 
it  is  associated  with  cleanliness.  Under  the 
influence  of  Koch,  people  became  accustomed 


THE    PREVENTION  OF   INFECTIOUS   DISEASE.   431 

to  the  idea  of  being  able  to  disinfect  without 
much  ado,  and  Fliigge  expressed  himself  very 
positively  in  regard  to  the  old  conception  that 
attached  importance  to  simple  filth  as  provo- 
cative of  disease.  The  view  held  by  Koch 
quickly  burned  itself  out.  We  are  able  to-day 
to  convince  ourselves  easily  that  Koch's  con- 
ception is  largely  mistaken.  Years  ago  I  de- 
fended the  contrary  view  in  the  words :  "  Dis- 
infection is  successful  only  where  cleanliness 
is  associated  with  it.  Cleanliness  is  the  first 
and  better  half  of  disinfection."  The  great 
disinfection  nuisance  of  1892  brought  the  real 
necessities  of  the  situation  again  to  the  reali- 
zation of  a  wide  circle.  At  that  time  even  the 
health  department  at  Berlin,  which  is  con- 
ducted under  the  influence  of  Koch,  had  to 
admit  that :  "  Cleanliness  is  better  than  poor 
disinfection. "  It  is  to  be  hoped  that  a  step 
further  will  be  taken,  and  that  the  authorities 
will  conclude  not  to  disinfect  at  all  except 
where  there  is  abundant  prospect  of  success. 
If  we  proceed  along  the  line  I  have  suggested, 
directions  for  disinfection  need  not  be  so  long 
that  we  forget  at  the  end  what  we  read  at  the 
beginning,  and  they  will  cease  to  be  official 
guides  to  abject  panic  and  fear  of  bacteria. 

Unfortunately   one    question    remains    but 
partly  solved.     In  the  recent  cholera  epidemic 


432  BACTERIOLOGY. 

in  Italy  in  the  last  decade,  and  again  in  1892, 
and  in  one  instance  also  in  Germany,  the  in- 
structions to  admit  foreign  goods  only  when 
disinfected  were  followed  literally,  and  im- 
ported disinfectants  were  disinfected.  Now 
the  question  is,  are  such  disinfectants  disin- 
fected and  made  impotent  by  disinfection  or  is 
their  efficacy  increased? 

In  the  presence  of  infectious  diseases  in  the 
neighborhood  or  in  one's  own  family,  disinfec- 
tion of  the  body  of  healthy  individuals  may  be 
brought  about  by  perfect  cleanliness  obtained 
by  the  use  of  warm  water  and  soap  ;  in  case  of 
direct  contact  with  contagious  disease  there 
must  be  added  the  washing  of  the  hands  with 
sublimate  or  solveol  (neutral  cresol).  Only  the 
germ  containing  substances  given  off  from  the 
sick,  such  as  sputum,  vomit  or  excreta,  all  of 
which  should  be  kept  in  a  moist  condition  and 
therefore  collected  in  vessels  containing  water, 
need  be  treated  with  disinfectants  of  a  kind  spe- 
cified as  suitable  by  the  physician  or  prescribed 
by  the  local  authorities.  Such  disinfectants  are 
carbolic  acid,  solutol  (alkaline  cresol)  or  fresh 
milk  of  lime.  The  vessels  are  then  to  be 
emptied  into  the  privy  where  the  bacteria  of 
putrefaction  will  care  for  the  remaining  germs 
more  effectively.  As  regards  many  of  the  de- 
tails of  the  earlier  and  mistaken  methods  of 


THE   PREVENTION   OF   INFECTIOUS   DISEASE.   433 

disinfection,  a  searching  criticism  supported 
by  abundant  material  will  be  found  in  the  sec- 
tion by  Else  Hueppe  in  our  work  upon  the 
cholera  epidemic  in  Hamburg  in  1892,  entitled, 
"  On  the  personal  care  of  health  and  the  nurs- 
ing of  the  sick."  Many  hospital  managements 
have  already  improved  their  instructions  in 
regard  to  disinfection  according  to  the  sug- 
gestions contained  in  this  paper. 

Disinfection  of  the  linen  of  the  sick  may  be 
accomplished  by  isolation  and  collection  of 
the  several  pieces  in  a  tub  of  water,  care  being 
taken  to  control  spilling.  The  individual 
pieces  are  then  rubbed  on  the  soiled  places  with 
soft  soap,  and  the  linen  is  rinsed  out  in  cold  alka- 
line soap  solution  and  well  boiled.  By  this 
process  disease  germs  are  destroyed.  If  the 
linen  is  first  placed  in  a  steam  disinfecting 
apparatus  the  specks  of  dirt  become  fixed  and 
the  value  of  the  linen  is  impaired.  Disinfec- 
tion of  linen  by  steam  is  therefore  to  be  limited 
to  cases  of  necessity.  On  the  other  hand  mat- 
tresses and  articles  of  clothing,  and,  when  pos- 
sible, furniture,  should  be  disinfected  in  the 
steam  apparatus. 

Daily  disinfection  of  the  sick-room  should, 
apart  from  the  essential  measure  of  admitting 
fresh  air  and  sunlight,  be  limited  to  wiping 

with  a  damp  cloth  the  dust  from  the  lower 
28 


434  BACTERIOLOGY. 

parts  of  the  walls,  from  the  doors  and  from  the 
floors.  After  the  sick-room  is  vacated  or  after 
death  has  occurred,  it  is  best  to  leave  the  room 
undisturbed  for  some  days  in  order  that  the 
germs  in  the  air  may  settle  down.  Then  the 
dust  may  be  removed  from  the  floor  and  the 
lower  part  of  the  walls  with  a  moist  cloth  ; 
after  that,  if  need  be,  the  floor  and  woodwork 
may  be  wiped  with  a  disinfectant.  Carpets 
may  be  cleaned  with  bread ;  the  particles  of 
dirt  and  the  bread-crumbs  that  fall  oft7  should 
be  carefully  taken  up  in  a  moist  condition  and 
burned ;  calcimined  walls  are  to  be  covered 
with  a  fresh  coat  of  lime-wash  when  it  is  neces- 
sary. The  best  means  of  disinfection  however 
are  always  to  be  found  in  light  and  air.  Pure 
outer  air  attenuates  to  a  state  of  impotency  the 
germs  present  in  a  room.  He  who  success- 
fully attacks  the  dread  of  light  and  fresh  air, 
and  effects  corresponding  improvements  in 
building  construction,  accomplishes  more  for 
an  effectual  disinfection  than  he  who  torments 
himself  with  the  ordinary  methods  .of  disinfec- 
tion and  the  inundation  of  dwellings  with  dis- 
infectants. 

Again,  in  the  separation  of  the  sick  from  the 
well  we  often  overshoot  the  mark,  and  the  com- 
pulsory conveyance  of  the  sick  from  dwelling- 
place  to  hospital  is  frequently  very  injurious. 


THE    PREVENTION    OF   INFECTIOUS   DISEASE.   435 

In  Hamburg  the  transportation  of  cholera 
patients  from  their  miserable  dwellings  to  a 
good  hospital  at  some  distance  was  not  borne 
very  well  by  the  patients  ;  on  this  account  the 
mortality  in  the  hospitals  was  greatly  in  excess 
of  the  average  mortality.  The  psychic  disad- 
vantages also  are  frequently  quite  considerable 
and  the  abolition  of  humanity  by  bacteriology 
seems  to  me  a  step  backwards.  I  discovered, 
— and  the  discovery  has  subsequently  been 
several  times  confirmed, — that  cholera  con- 
valescents, even  after  they  have  perfectly  re- 
gained their  health,  may  still  harbor  cholera 
germs  for  weeks  ;  and  according  to  Rumpel, 
both  during  and  after  an  epidemic,  completely 
healthy  individuals  may  harbor  such  germs  ; 
diphtheria  convalescents  also  may  for  months 
carry  about  diphtheria  bacilli,  and  this  may  oc- 
cur too  in  healthy  individuals.  On  account  of 
these  facts  compulsory  isolation  upon  the  basis 
of  bacteriological  findings  may  lead  to  the 
greatest  injury.  It  has  been  shown  by  actual 
examination  that  it  is  highly  improbable  that 
any  considerable  number  of  new  contagions 
follow  in  the  train  of  those  healthy  individuals 
and  convalescents  in  whom  bacteria  are  found. 
The  imprisonment  of  healthy  and  convalescent 
individuals  is  an  inadmissible  restriction  of 
personal  freedom. 


436  BACTERIOLOGY. 

The  ways  in  which  disease  is  generally  dis- 
seminated speak  also  against  bacteriological 
excesses.  In  India  mere  removal  of  the  place 
of  encampment  has  always  proved  an  impor- 
tant means  of  protection  against  cholera  and 
such  removal  does  not  threaten  the  new  neigh- 
borhood with  the  disease.  The  German  mili- 
tary hospital  at  Metz  has  acted  upon  the  sur- 
rounding conditions  of  health  only  in  a  favor- 
able way  and  has  not  conduced  to  the  spread 
of  typhoid  fever  and  diarrhoea. 

In  diseases,  too,  of  the  character  of  scarlet 
fever  we  have,  to  the  delight  of  the  martinets, 
done  too  much  in  the  last  decade  in  the  matter 
of  isolation.  In  all  these  matters,  after  giving 
bacteriology  its  due,  greater  value  must  again 
be  attached  to  medical  experience.  The  ad- 
vance in  the  science  itself  has  frequently  led  to 
a  change  of  view  from  the  extreme  claims  of 
Koch  and  has  confirmed  the  wisdom  of  the 
moderate  conceptions  of  the  English.  In 
most  cases  bacteriology  has  led  us  to  the  same 
conclusions  as  epidemiolog}^  A  method  of 
combating  disease  which  does  not  adjust  itself 
to  our  "modern  social  conditions  both  industrial 
and  social  is  worthless  from  the  beginning. 
The  colossal  injury  to  trade  and  commerce 
wrought  by  cholera  in  1892  abundantly  showed 
that  the  way  of  fighting  disease  then  employed 


THE   PREVENTION   OF   INFECTIOUS   DISEASE.    437 

does  only  harm,  while  a  preventive  method  is 
perfectly  feasible  and  would  not  paralyze  the 
industry  of  the  country.  Control  of  cholera 
by  a  milder  system  has  proved  to  be  the  only 
truly  effective  proceeding.1 

The  campaign  against  disease  germs  and 
their  diffusion  is  not  without  good  prospects 
of  success.  This  campaign  must  be  directed 
also  toward  securing  the  prevention  of  disease, 
since  we  are  limited  by  social  conditions  in  at- 
tempting to  apply  the  method, — more  correct 
in  principle, — of  the  destruction  of  the  predis- 
position to  disease.  But  the  campaign  against 
germs  can  succeed  without  involving  us  in 
any  trenchant  resistance  to  the  modern  social 
order.  It  is  the  duty  of  really  civilized  states 
to  create  conditions  suitable  to  aid  in  this  un- 
dertaking. This  duty  consists  in  the  reform 
of  the  sanitary  conditions  upon  the  basis  of  the 
theory  and  practice  of  public  health.  "  It  is," 
says  Sonderegger,  "  a  momentous  error  to  be- 
lieve that  any  sanitary  police  system,  no  matter 
how  carefully  conducted,  can  be  of  any  use 
where  practices  conducive  to  the  public  health 
are  neglected." 

1  A  most  disgraceful  case  of  the  application  of  extreme  bacterio- 
logical notions  to  the  combating  of  disease  may  be  found  in  the  fact 
that  a  few  years  ago  even  half-civilized  and  barely  tolerated  minia- 
ture states  of  the  east  like  Bulgaria  had  the  effrontery,  on  the  break- 
ing out  of  cholera,  to  impose  a  scandalous  blockade  against  the  large 
European  states. 


438  BACTERIOLOGY. 

But  just  because  these  solid  foundations  are 
frequently  lacking  and  because  the  circles  of 
government  officials  are  not  yet  in  full  posses- 
sion of  the  facts,  the  ministers  of  finance,  em- 
powered to  make  the  great  expenditures  of 
civilization,  do  not  wish  to  disburse  much 
money  for  this  purpose,  and  in  our  municipali- 
ties more  politics  than  political  economy  is 
practiced.  Upon  the  continent  of  Europe  the 
authorities  are  very  quick  to  adopt  sanitary 
police  measures  and  mutually  supporting  or- 
dinances. Police  regulations  are  especially 
welcomed  in  those  places  where  the  will  and 
the  creative  capacity  for  social  reforms  are 
lacking.  By  such  measures,  however,  atten- 
tion is  merely  directed  to  the  fact  that  a  sani- 
tary organization  on  the  basis  of 'hygiene  and 
adapted  to  the  need  of  the  times  is  still  an 
urgent  want. 

A  simplification  of  the  statistics  of  sickness 
and  death  is  an  imperative  step  in  the  accom- 
plishment of  any  measures  of  reform.  This 
can  only  be  brought  about  by  the  help  of 
practicing  physicians.  For  this  purpose  the 
schemata  must  be  very  concise  and  no  difficul- 
ties in  respect  to  their  transmission  by  post 
should  be  imposed.  Especially  in  times  of 
epidemic  physicians  have  more  to  do  than  to 
satisfy  the  curiosity  of  red-tape  statisticians. 


THE   PREVENTION    OF   INFECTIOUS   DISEASE.   439 

Physicians  have  no  energy  or  time  to  be  wasted 
in  doing  a  favor  to  the  association  for  the 
benefit  of  paper  manufacturers  which  is  so 
firmly  established  in  bureaucracy.  But  it  is 
indispensable  that  by  simple  participation  of 
the  attendant  physicians,  and  by  reliable 
coroners'  inquests,  a  correct  and  speedy  notifi- 
cation and  enumeration  of  the  cases  of  infec- 
tious diseases  be  made  possible,  while  the  inter- 
ference of  official  physicians  in  private  affairs 
is  entirely  inadmissible  and  contrary  to  our 
Germanic  notions  of  law.  Even  legislation 
must  make  allowance  for  the  awakening  rec- 
ollection of  our  own  nationality.  Those  fine 
times  are  past  when  the  appointed  authorities 
were  able  to  direct  the  local  physicians  to  cause 
the  epidemic  to  cease  since  it  had  lasted  long 
enough. 

In  spite  of  this  progress  the  administration 
is  still  guided  too  little  by  actual  conditions. 
A  gratifying  change  of  opinion  however,  in 
which  we  see  at  work  the  influence  of  bacteri- 
ological discoveries,  is  already  to  be  noted. 
That  the  prevention  of  infectious  disease  by 
combating  the  cause  of  the  disease  is  a  great 
social  achievement  cannot  be  denied. 


CHAPTER  VIII. 

THE   HISTORY   OF   BACTERIOLOGY. 

MEN  justly  attempt  to  understand  what  at 
present  exists  by  considering  the  manner  in 
which  it  has  come  into  existence,  and  we  are 
hence  in  the  habit  of  drawing  up  an  historical 
outline  of  any  subject  we  may  be  carefully 
considering.  In  bacteriology,  however,  we 
have  been  for  some  time  engaged  in  a  com- 
plete revaluation  of  our  data.  The  old  facts 
remain,  but  new  facts  have  been  added  to  them 
with  the  result  of  bringing  to  maturity  new 
theories.  These  have  either  not  conformed  at 
all  to  ideas  generally  received  or  have  perhaps 
fallen  in  with  older  views  which  had  been  ap- 
parently set  aside.  Under  such  circumstances 
it  is  best  first  of  all  to  learn  to  know  the  data 
now  at  our  disposal  in  order  to  consider  as  ob- 
jectively as  possible  the  facts  and  theories  of 
an  earlier  time. 

Knowledge  of  the  occurrence  of  poisonous  in- 
sects such  as  mosquitos  and  tse-tse  flies  led  peo- 
ple of  the  older  civilizations  to  an  ontological 

conception  which  set  up  Beelzebub  as  the  supe- 
440 


THE   HISTORY   OF  BACTERIOLOGY.  441 

rior  god  or  patron  of  the  invisible  or  visible  poi- 
sonous flies  that  brought  disease.  The  Roman 
writer  Varro  supposed  in  like  fashion  that,  as 
we  recognize  with  the  naked  eye  both  large 
and  small  insects  hovering  over  the  marshes,  so 
insects  still  smaller  are  able  to  exist,  and  these 
forms,  so  small  as  to  be  invisible,  might  per- 
haps be  the  cause  of  marsh  fever ;  previous  to 
this  men  had  usually  looked  upon  emanations 
or  injurious  gaseous  substances  as  the  cause  of 
this  fever.  Paracelsus  had  a  dim  foreshadowing 
of  the  truth  when  he  spoke  of  the  "  seeds  "  of 
disease.  The  Jesuit  Kircher,  from  observations 
upon  the  process  of  putrefaction  and  the  worms 
which  made  their  appearance  in  the  course  of 
this  process  and  which  he  observed  with  a 
poor  little  microscope  was  the  first  to  develop 
in  a  very  comprehensive  fashion  the  theory 
of  a  "  contagium  animatum  r>  (1671).  Van 
Leeuwenhoek,  the  "  father  of  micrography," 
was,  however,  the  first  really  to  discover  the 
' '  world  of  the  infinitely  little. "  He  worked  dur- 
ing the  last  quarter  of  the  iyth  century,  with 
the  help  of  a  good  microscope  that  he  himself 
constructed,  and  studied  the  organisms  found 
in  infusions,  putrefying  fluids,  pus  and  other 
substances.  Among  the  organisms  that  he  ob- 
served and  noted  were  those  we  now  know  as 
bacteria,  then  perceived  for  the  first  time. 


442  BACTERIOLOGY. 

Leeuwenhoek's  successors  busied  themselves 
with  describing  and  classifying  these  u  infu- 
sion animals."  Among  these  investigators  are 
especially  to  be  mentioned  v.  Gleichen-Russ- 
worm  (1778)  and  Otto  Friedrich  Miiller 
(1786),  the  latter  of  whom  made  good  drawings, 
applied  many  of  the  names  we  still  use  and 
established  genera  still  recognized.  Bory  de 
St.  Vincent  (1824)  made  a  further  advance, 
and  in  1838,  Ehrenberg,  and  in  1841,  Dujardin' 
followed  with  new  discoveries,  which  were 
added  to  in  1852  by  Pert/y  and  in  1853  by  Ferdi- 
nand Colin.  In  opposition  to  their  predeces- 
sors these  later  investigators  reckoned  bacteria 
among  the  true  plants  and  Perty  clinched  the 
demonstration  by  the  discovery  of  endogenous 
spore-formation. 

Cohn  sought  to  develop  the  systematic 
classification  of  bacteria.  He  carried  out  a 
system  of  separation  into  many  genera  and 
species,  laying  stress  upon  the  differences  ob- 
served. Perty  recognized  clearly  the  occur- 
rence of  a  variation  in  form  according  to  the 
substratum,  whereas  before  this  there  had  been 
simply  a  general  recognition  of  a  Protean-like 
change  of  form. 

From  the  time  of  Kirch er  onward,  the  doc- 
trine of  a  "  contagium  animatum"  went  hand 
in  hand  with  the  amassing  of  this  systematic 


THE   HISTORY   OF   BACTERIOLOGY.  443 

knowledge.  Among  others  Lancisi,  Reau- 
mur, Linne"  and  Plenciz  gave  their  adhesion 
to  the  theory,  Plenciz  in  1762  advancing  com- 
prehensive reasons  for  it.  The  investigations 
of  Pringle  upon  infectious  diseases  and  disin- 
fectants also  belong  to  this  period.  The  doc- 
trine, however,  soon  became  discredited,  be- 
cause of  the  growth  of  the  opinion  that  not 
merely  the  causers  of  disease  were  alive  and 
parasitic,  but  the  diseases  themselves  were 
parasites ;  names  like  lupus  and  cancer  still 
remind  us  of  this.  Of  even  greater  influence 
was  the  fact  that  the  study  of  pathological 
anatomy  under  Malpighi,  Bichat  and  Virchow 
busied  itself  only  with  the  consideration  of  the 
anatomical  changes  in  disease,  and  lost  all 
comprehension  of  the  outside  factors.  This 
went  so  far  that  only  in  1874  did  Virchow 
express  a  very  restricted  recognition  of  the 
parasitic  theory  of  infectious  disease. 

The  question  how  far  microbes  are  con- 
cerned in  the  processes  of  putrefaction  and 
fermentation  approached  the  matter  on  quite 
another  side.  Some  asserted  that  the  infu- 
soria and  moulds  on  account  of  their  ubiquity 
were  a  ^v^oo^a  naxov  jSoro?,  a  bad  fermentation 
product  of  the  soil,  originated  by  spontaneous 
generation,  while  others  derived  them  legiti- 
mately from  germs  of  the  same  kind.  Micheli 


444  BACTERIOLOGY. 

succeeded  as  early  as  1729  in  cultivating  many 
moulds  from  spore  to  spore.  So  far  as  the 
smut  and  rust  fungi  were  concerned,  however, 
origin  by  heterogenesis  seemed  still  possible 
till  in  1801,  Persoon,  and  in  1853  De  Bary 
solved  this  question  finally.  The  notion  of 
the  spontaneous  generation  of  insects  was 
overthrown  by  Swammerdam  (1669)  and  Redi 
(1688),  so  that  the  supporters  of  this  doctrine 
were  forced  to  have  recourse  to  still  smaller 
organisms.  Needham  believed  that  he  could 
prove  experimentally  the  spontaneous  genera- 
tion of  "infusion  animals"  and  his  conclu- 
sions met  with  general  assent  for  a  time,  but 
Bonnet  (1762)  and  Spallanzani  (1769)  over- 
threw his  claim  so  completely  that  Appert 
(1809)  was  able  to  devise  a  successful  method 
for  the  preservation  of  food  materials  on  the 
basis  of  their  work.  This  was  the  first  practi- 
cal result  of  the  older  bacteriology.  New  op- 
ponents continued  to  arise  till  Franz  Schulze 
(1836),  Schwann  (1837),  Schroeder  and  v. 
Dusch  (1854-1861),  van  der  Broek  (1857)  and 
Pasteur  (from  1857  onwards)  overthrew  by  con- 
clusive evidence  every  argument  for  spontane- 
ous generation,  and  demonstrated  that  all  mi- 
crobes arise  by  legitimate  descent  out  of  germs 
of  the  same  kind.  The  doctrine  of  spontane- 
ous generation  became  in  the  hands  of  Bechamp 


THE   HISTORY   OF   BACTERIOLOGY.  445 

the  doctrine  of  microzymes,  that  is  of  the 
origination  of  active  granules  in  the  living 
organism  ;  in  the  hands  of  Wigand  it  became 
the  doctrine  of  the  anamorphosis  of  protoplasm, 
that  is,  of  the  transformation  of  higher  cell 
protoplasm  into  bacterial  protoplasm  ;  and  in 
those  of  Fokker,  the  similarly  conceived 
doctrine  of  heterogenesis.  The  kernel  of 
truth  in  the  whole  matter  is  that  there  really 
are  cellular  elements  whose  activity  lasts 
longer  than  the  life  of  the  cell.  All  the  effects 
of  this  sort  are  in  the  same  class  with  the 
power  manifested  by  the  "  active  "  proteid  se- 
creted by  the  gland-cells  in  the  form  of  the 
solvent  enzymes  ;  these  enzymes  often  appear 
as  cell  granules  which  have  outlived  the  cell 
and  have  become  independent,  but  they  only 
display  part  of  the  cell  activities,  and  are  not 
capable  of  forming  new  cells. 

If  the  "  infusion  animals," — and  in  this 
group  were  included  the  organisms  we  to-day 
call  bacteria, — could  not  arise  in  albuminous 
fluids  by  spontaneous  generation,  but  could 
spring  only  from  germs  of  their  own  kind 
which  had  somehow  made  their  way  into  the 
fluids,  then  on  the  other  hand  it  must  be  as- 
sumed that  the  germs  in  proportion  as  they 
multiplied  would  evoke  various  decompositions 
by  virtue  of  their  life  activities.  This  was 


44-6  BACTERIOLOGY. 

shown  by  Astier   in   1813    in  regard   to  the 
yeasts,  and  by  Sette  in  1819  in  the  case  of  the 
microbe  of  the  bleeding  host,   but   Cagniard 
de  Latour  and  Schwann  were  the  first  to  suc- 
ceed in  bringing  proof  for  this  view  and  proof 
which  was  of  so  satisfactory  a  kind  that  Turpin 
in  the  following  year  attributed  all   fermenta- 
tions to  the  life  of  microbes.     These  experi- 
ments were  in   1841  supplemented  by  Fuchs 
with   experiments  upon  blue  milk,  and  again 
by  Remak  in  1841,  and  Mitscherlich  in  1841- 
1843,  each  of  these  observers  finding  different 
kinds  of  ferment  organisms  in  different  fer- 
mentations.      Helmholtz    in   1843    made  im- 
portant observations  upon  the  germs  of  putre- 
faction.    It  was  however  in  the  years  following 
1857  that  Pasteur  finally  established  the  truth 
of  the  view  that  all  processes  of  fermentation 
and  putrefaction  alike  are  caused  by  living 
things,    and   that  in   each    different   fermen- 
tation  different   kinds    of   microbes    are  con- 
cerned.    The  specificity  of  the  ferment  germ 
appeared  according  to  his  investigations  to  be 
the  cause  of  the  typical  specific  fermentations. 
Goeze  and  Bremser's  study  of  the  develop- 
ment of  tapeworms  afforded  insight  into  the 
cause    of    tapeworm    and   pinworm    diseases. 
Then   Prevost  (1807)  discovered  that  moulds 
are  the  cause  of  many  plant  diseases,  and  this 


THE    HISTORY    OF   BACTERIOLOGY.  447 

work  reached  a  positive  conclusion  when  De 
Bary  proved  that  parasitic  moulds  occurring 
upon  different  plants,  and  till  then  regarded 
as  different  species,  belong  in  the  cycle  of 
development  of  a  single  species,  and  showed 
that  such  a  change  of  host  or  hetercecism 
took  place  among  the  rusts  or  Uredineae. 
Bassi  and  Balsamo  discovered  in  1835  (pub- 
lished in  1837)  that  the  disease  of  silkworms 
known  as  muscardine  is  caused  by  a  mould, 
and  Audouin  found  that  this  mould  forms 
spores,  by  the  help  of  which  the  germs  of  the 
disease  live  through  the  winter  and  are  able 
to  spread  the  disease  anew  the  next  year. 
Schoenlein  discovered  the  mould  that  causes 
scald-head  in  1839.  At  the  same  time  the  itch- 
mites  were  discovered  anew. 

On  the  basis  of  these  discoveries  regard- 
ing the  processes  of  fermentation  and  disease, 
Eisenmann,  and  still  more  acutely  Henle, 
again  urged  (1840)  the  doctrine  of  a  con- 
tagium  animatum,  and  with  such  success 
that  in  spite  of  Virchow's  opposition  the  doc- 
trine henceforward  never  disappeared  from 
the  order  of  the  day.  Another  thing  contrib- 
uted also  to  the  establishment  of  this  doctrine, 
namely,  that  the  need  of  assuming  external 
causes  of  disease  was  making  itself  felt  among 
epidemiologists.  Pettenkofer  especially,  from 


448  BACTERIOLOGY. 

1854  onwards,  developed  the  view  that  a  dis- 
tinction must  be  made  between  those  disease 
germs  which  develop  endogenously  only  in  sick 
men  and  those  which  reproduce  themselves 
ectogenously  outside  of  the  human  body.  The 
experiments  begun  in  1857  by  Semmelweiss 
upon  the  prevention  of  childbed  fever  by 
keeping  away  decomposable  substances,  and 
those  by  Lemaire  in  1860,  who  proved  that 
carbolic  acid  annulled  the  action  only  of  living 
germs  and  not  of  enzymes,  were  recognized  to 
be  of  great  importance. 

But  direct  discoveries  also  were  not  lacking. 
Pollenderin  1849  an^  Davaine  and  Rayer  in 
1850  discovered  the  anthrax  bacteria.  The 
etiological  significance  of  the  germs  was 
clearly  pointed  out  by  Davaine  about  1863, 
and  in  1877  Koch,  by  the  discovery  of  the 
spores,  brought  the  question  to  a  satisfactory 
conclusion,  as  in  earlier  times  Audouin  had 
rendered  complete  the  discovery  of  Bassi.  A 
similar  discovery  was  made  by  Pasteur  in  1865 
in  another  disease  of  silkworms,  pebrine, 
which  he  likewise  brought  to  a  satisfactory 
conclusion  by  the  demonstration  of  spores. 
Obermeier  in  1873  discovered  the  Spirochaete 
of  relapsing  fever.  Von  Recklinghausen, 
Waldeyer,  Klebs  and  Weigert  had  already 
found  bacteria  in  the  tissues  in  various  dis- 


THE   HISTOBY   OF   BACTERIOLOGY.  449 

eases,  when  Koch  in  1878  published  his 
investigations  upon  wound  infections.  Ac- 
cording to  his  conclusions  every  special  dis- 
ease had  corresponding  to  it  a  special 
disease  germ  just  as  there  appeared  to  be  a 
special  germ  for  each  fermentation.  Pasteur's 
comprehensive  work  laid  the  foundation  for  the 
conception  that  each  special  fermentation  and 
disease  was  causally  dependent  upon  a  special 
micro-organism,  and  Koch's  work  capped  this 
view  just  as  comprehensively. 

This  idea  corresponded  so  admirably  with 
the  general  expectations  of  a  physician  brought 
up  on  ontological  conceptions  that  in  the  imme- 
diate future  the  wish  became  father  to  the 
thought.  Koch  advanced  this  line  of  work  in 
a  remarkable  degree  by  the  methods  he  de- 
vised about  1880.  The  isolation  of  pure  cul- 
tures of  a  large  number  of  micro-parasites  was 
achieved  and  in  many  cases  it  was  demon- 
strated by  successful  transfer  to  animals,  that 
the  microbes  had  great  significance  in  the 
origination  of  those  diseases  in  which  they 
were  observed  (cf.  Chapter  III.,  p.  87).  In 
this  series  of  investigations,  Koch's  discovery 
in  1882  of  the  germ  of  tuberculosis  stands  out 
conspicuously  as  especially  epochal.  This  is 
indeed  the  greatest  discovery  due  to  the  carry- 
ing out  of  a  method  which  has  as  yet  been 
29 


45O  BACTERIOLOGY. 

made  in  bacteriology.  Even  the  discovery  of 
the  cholera  bacteria  in  1884  by  Koch  and  his 
co-workers  Gaffky  and  Fischer  was  of  less 
importance  because  of  the  fact  that  this  in- 
vestigation was  not  brought  to  a  satisfactory 
termination ;  indeed,  Lister  in  1891  at  the 
International  Congress  in  London  declared 
that  the  etiological  significance  of  the  comma 
bacilli  first  became  admissible  through  the 
proof  brought  by  Hueppe  of  the  formation  of 
poison.  (That  the  parasitic  bacteria  exert  their 
effect  through  the  formation  of  poison  has  been 
set  forth  fully  in  preceding  sections.)  Along 
this  line  of  work  there  is  as  yet  no  proof  that 
micro-parasites  occur  as  the  exciting  cause  of 
the  typical  acute  exanthemata  like  small-pox, 
typhus  fever,  scarlet  fever  and  measles.  It  is 
certainly  striking  that  the  results  up  to  the 
present  time  should  be  negative  in  just  those 
diseases  most  markedly  contagious,  and  this 
is  perhaps  explicable  on  the  supposition  that 
bacteria  are  not  concerned  in  these  affections. 
Enlightenment  as  to  the  germs  causing 
malignant  tumors,  especially  the  epithelial 
tumors  and  among  them  the  carcinomas  would 
be  equally  desirable.  The  objects  that  have 
up  to  the  present  been  described  as  the  para- 
sites of  carcinoma  will  not  stand  criticism. 
Important  reasons,  moreover,  are  adduced  for 


THE    HISTORY   OF   BACTERIOLOGY.  451 

the  view  that  these  tumors  are  perhaps  not  to 
be  attributed  at  all  to  micro-parasitic  cause, 
and  hence  very  stringent  proof  is  necessary  to 
produce  conviction  on  this  point. 

The  whole  tendency  to  search  out  "  specific  " 
germs  of  disease  and  fermentations  is  a  relic 
of  the  natural  history  point  of  view.  The  no- 
tion that  every  specific  disease  is  caused  by  a 
specifically  constant  parasite  is  in  accordance 
with  the  ontological  wish  of  many  physicians 
who  are  thus  spared  the  trouble  of  further  re- 
flection. There  is,  in  addition,  the  fact  that  in 
courses  of  instruction  we  are  compelled  first  to 
convey  to  pupils  in  a  methodical  manner  and 
by  concrete  examples  a  general  understand- 
ing of  fazcontagium  animatum.  An  introduc- 
tion to  the  subject  matter  starts  necessarily 
from  the  specificity  of  the  microbes.  In  the 
brief  time  at  the  disposal  of  most  students  they 
usually  do  not,  on  the  basis  of  their  own  ob- 
servations, pass  beyond  this  stage,  so  that  the 
courses  in  bacteriology  have  aided  largely  in 
bringing  it  about  that  this  ontological  and  thor- 
oughly unscientific  conception  of  the  relations 
of  bacteria  to  disease  has  become  the  common 
property  of  physicians.  A  pedagogical  neces- 
sity has  thus  directly  contributed  to  impair 
the  scientific  training  of  physicians. 

It  is  a  false  premise  that  the  constancy  of 


452  BACTERIOLOGY. 

species,  the  specificity  of  the  parasitic  mi- 
crobes is  the  cause  of  disease.  As  Henle  de- 
duced the  etiology  •  of  disease  from  the  con- 
stancy of  the  specific  disease  germs,  so,  in 
association  with  Perty,  Billroth  and  Nageli 
have  just  as  logically  developed  the  view 
that  the  bacteria  vary  and  adapt  them- 
selves both  in  form  and  action  to  the  condi- 
tions of  existence.  Both  investigators  over- 
shot the  mark,  for  Billroth  assumed  the 
existence  of  only  one  pathogenic  species  which 
he  called  Cocco bacteria  septica,  and  Nageli 
recognized  no  constant  species  outside  of 
Sarcina. 

Hans  Buchner  as  far  back  as  1878  treated 
the  virulent  anthrax  germ  culturally  in  such 
a  way  that  it  became  impotent ;  unfortunately 
in  1880  he  went  still  further,  supposing,  in 
accord  with  Nageli's  idea,  that  by  cultivation 
he  transformed  the  pathogenic  anthrax  bacil- 
lus into  the  saprophytic  hay-bacillus  and  vice 
versa.  Koch  also  went  too  far  in  his  criticism 
when  he  assumed  that  Buchner  simply  con- 
founded these  very  different  species  of  bacteria. 
Prazmowsky  and  De  Bary  have  found  that  at- 
tenuated anthrax  bacteria  at  times  really  form 
pellicles  on  the  surface  of  fluids  like  the  hay 
bacillus.  It  is  impossible,  however,  by  cultiva- 
tion to  change  one  kind  into  the  other,  and  the 


THE   HISTORY   OF  BACTERIOLOGY.  453 

germination  of  spores  in  the  two  species  is  very 
different  (Prazmowsky  and  Brefeld).  Never- 
theless Buchner  intentionally  and  with  a  clear 
understanding  of  his  aim  attempted  to  influ- 
ence the  disease-producing  activity  of  the  par- 
asite, which  was  the  factor  considered  by  Koch 
as  causal  and  necessarily  constant,  and  this 
result  he  was  the  first  within  certain  limits  to 
achieve.  A  similar  result  was  accidentally 
obtained  in  1880  by  Pasteur,  who  found  that 
virulent  cultures  of  the  bacteria  of  chicken 
cholera  become  impotent  after  standing  for 
some  time  in  the  air.  From  this  discovery  by 
Buchner  and  Pasteur  we  may  date  a  new  period, 
the  scientific  epoch  in  bacteriology.  If  we  are 
able  at  will  to  diminish  or  altogether  annul 
the  most  important  characteristic  of  bacteria 
and  the  one  formerly  supposed  to  be  necessarily 
constant,  that  is  the  "  specific  "  ability  to  pro- 
duce "  specific  "  diseases,  fermentations,  putre- 
factions or  pigments,  and  on  the  other  hand  to 
heighten  this  power,  then  we  must  change  our 
whole  conception  of  causal  relationship.  By 
means  of  artificial  protective  inoculations  such 
as  Pasteur  in  1880  undertook  for  the  first  time 
with  the  attenuated  bacteria  of  chicken  cholera, 
the  whole  realm  of  experimentation  became 
accessible. 

These   investigations   caused   stress  to   be 


454  BACTERIOLOGY. 

laid  again  upon  the  significance  of  the  animal 
organism  in  the  etiology  of  the  infectious  dis- 
eases, in  predisposition  toward  disease,  in  nat- 
ural immunity  and  in  immunization,  although 
the  correct  etiological  interpretation  was  not 
immediately  perceived.  H.  Buchner  and  Met- 
schnikoff  especially  furnished  important  aid  in 
this  work,  and  Hueppe  in  1893  maintained  in 
a  purely  mechanical  and  monistic  fashion  and 
in  a  manner  free  from  all  ontology  the  causal 
continuity  existing  in  infectious  diseases  and 
thus  did  away  with  the  last  remnant  of  ontol- 
ogy, even  in  the  complicated  realm  of  organic 
science.  In  this  scientific  conception  of  etiol- 
ogy lies  the  final  reconciliation  between  cellu- 
lar pathology  and  bacteriology,  a  reconciliation 
which  could  not  and  would  not  be  brought  about 
previously  because  each  of  these  conceptions  in 
its  ontological  relations  held  only  its  own  idol 
worthy  of  worship.  With  the  removal  of  this 
remnant  of  ontology  went  the  last  reminder  of 
the  personifications  of  priest  medicine.  The 
abandonment  of  every  form  of  ontology  makes 
it  possible  for  medicine  to  develop  in  as  strictly 
a  mechanical  way  as  any  other  natural  science. 
Although  medicine  has  been  greatly  preoc- 
cupied with  bacteria,  bacteriology  has  till  now 
exerted  only  a  very  slight  influence  upon  med- 
ical thought.  For  the  majority  of  physicians 


THE    HISTORY   OF   BACTERIOLOGY.  455 

it  has  happened  merely  that  one  disease  entity, 
the  diseased  cell,  has  been  replaced  by  another 
disease  entity,  the  pathogenic  bacillus.  On  the 
basis  of  such  a  conception,  however,  thousands 
of  observations  upon  healthy  and  diseased 
human  beings  remain  irreconcilable  and  just 
as  little  capable  of  comprehension  as  before. 
Only  on  a  conception  not  ontological,  but  me- 
chanical or  dynamical,  forming  a  part  of  the 
monistic  conception  of  the  universe,  will  all 
discoveries  be  made  more  intelligible  ;  and  the 
variable  as  well  as  the  constant  will  find  its 
place,  the  mysticism  of  ontology  having 
been  taken  away  from  both.  By  advanc- 
ing this  scientific  conception  bacteriology  is 
qualified  to  influence  medical  thought  favor- 
ably and  to  render  it  essentially  more  pro- 
found. 

Bearing  this  possibility  in  mind  the  position 
of  scientific  bacteriology  in  medicine  and 
hygiene  is  sharply  and  clearly  defined.  As  I 
have  tried  to  show  connectedly  in  the  present 
work,  the  striving  of  scientific  medicine  after 
unity  finds  in  this  scientific  exposition  of 
bacteriology  a  clear  and  comprehensive  ex- 
pression. 


BIBLIOGRAPHY. 


THE  large  number  of  bacteriological  papers  that 
appear  in  the  coarse  of  a  year,  and  the  scattering  of 
the  records  of  research  in  different  periodicals  have 
brought  into  existence  certain  publications  which  make 
a  specialty  of  recording  and  summarizing  all  the  more 
important  contributions.  Baumgarten's  Jahresbericht 
uber  die  Fortschritte  in  der  Lehre  von  den  pathogenen 
Mikroorganismen  is  one  of  the  most  comprehensive  of 
these,  but  is  usually  late  in  appearing.  Alfred  Koch's 
Jahresbericht  uber  die  Fortschritte  in  der  Lehre  von  den 
Gdhrungsorganismen  covers  a  somewhat  different  field, 
and  deals  more  with  the  general  biological  side  of 
bacteriology.  The  Hygienische  Rundschau  (bi-weekly), 
and  the  Centralblalt  fur  aUgemeine  Gesundheitspflege 
(monthly)  include  especially  matter  bearing  on  the 
hygienic  aspects  of  the  subject. 

The  Centralblatt  fur  Bakteriologie,  Parasilenkunde  und 
Infektionskrankheiten  is  the  most  important  aid  in 
keeping  abreast  of  current  progress.  At  the  beginning 
of  1895  the  scope  of  this  journal  was  somewhat  broad- 
ened, and  a  division  of  territory  made,  the  journal  being 
now  issued  in  two  sections,  one  dealing  with  the  medi- 
cal and  hygienic  side  :  Abtheilung  I.,  Medizinisch- 
hygienische  Bakleriologie  und  tierische  Parasitenkunde 
(2  volumes  yearly,  15  marks  a  volume);  andtheother 
with  the  general  biological  and  technological  side  : 
Abtheilung  II.,  Allgemeine,  landwirtschaftlich  techno- 

457 


458  BIBLIOGRAPHY. 

logische  Bakteriologie,    Gdrungs physiologic   and  Pflan- 
zenpathologie  (i  volume  yearly,   16  marks). 

The  chief  journals  in    which  the  results  of  original 
research  are  published  are  the  following : 
Zeitschrift  fiir  Hygiene  und  Infedionskrankheiten  (edited 

by  R.  Koch  and  C.  Fliigge). 
Annales  de  llnslitut  Pasteur  (Duclaux). 
Arbeiten  aus  dem  kaiser  lichen  Gesundheitsamte. 
Archiv  fur  Hygiene  (Pettenkoter). 
Annales  de  Micrographie  (Miquel). 

Journal  of  Pathology  and  Bacteriology  (Sims  Woodhead). 
Journal  of  Experimental  Medicine  (Welch). 

Many  important  papers  appear  also  in  the  various 
medical  journals  and  in  periodicals  devoted  mainly  to 
pathology  or  hygiene.  Several  important  discoveries 
have  been  first  announced  through  the  Deutsche  medi- 
cinische  Wochenschrift. 

The  following  reference  manuals  and  general  text- 
books may  be  mentioned  : 

Abbott.      Principles  of  Bacteriology.      4tfi  Ed. ,   1897. 
Baumgarten.     Lehrbuch  der  pathologischen  Mykologie, 

1886-90. 

v    Corn il  et  Babes.     Les  Bacteries,  3d  Ed. ,    1890. 
t     Crookshank.      Bacteriology  and  Infective  Diseases,  1896. 
1     Duclaux.      Traite  de  Microbiologie,  I.,  1897. 
»'   Fischer.       Vorlesungen  uber  Baklerien,    1897. 
i/   Fliigge.      Die  Mikroorganismen,  3.  Aufl. ,  1896. 

Frankel,  C.  Grundriss  der Bakterienkunde,  3.  Aufl.  ,1890. 
Giinther.  -  Einfiihrung   in   das  Sludium  der    Bakterio- 
logie.    4.  Aufl.,  1895. 
v    Heirn.     Lehrbuch  der  bakteriologischen    Untersuchung 

und  Diagnostik,  2.  Aufl.,  1898. 

•     Hueppe.       Die   Methoden    der   Bakterienforschung,  5. 
Aufl.,  1891. 


BIBLIOGRAPHY.  459 

Kanthack  and  Drysdale.      Practical  Bacteriology ,   1895. 
Klein.      Microorganisms  and  Disease,  3<lEd.,   1896. 
M'Farland.       Text-book  upon  the  Pathogenic  Bacteria, 

1896. 

Migula.     System  der  Bakterien,  Bd.  I.,  1897. 
Muir  and  Ritchie.      Manual  of  Bacteriology,    1897. 
Thoinot  and  Masselin.      Precis    de  Microbie,   3d    Ed., 

1896. 

Schenk.      Grundriss  der  Bakteriologie,   1892. 
Sternberg.      Manual  of  Bacteriology,  2d  Ed.,   1896. 
Woodhead.     Bacteria  and  their  Products,   1891. 

Works  dealing  more  particularly  with  the  industrial 
side  of  bacteriology  are  : 
Conn.      The  Fermentations  of  Milk,  1892. 
Freudenreich,   E.  v.     Die  Bakteriologie   in    der   Milch- 

wirtschafi,    1893. 
Grotenfelt-Woll.       The    Principles    of   Modern   Dairy 

Practice,  1894.  , 

Kramer.     Die  Bakteriologie  und  ihre  Beziehungen  zur 

Landwirtschaft,    1890-2. 

Lafar.      Technical  Mycology.      Eng.  trans.,  1898. 
Migula.      Bakterienkunde  fiir  Landwirthe,  1890. 
Pearmain  and  Moor.     Applied  Bacteriology,    1896. 
Russell,  H.  L.     Outlines  of  Dairy  Bacteriology,  1894.    . 
Sch oil.     Die  Milch ,  1891. 

Valuable  special  bibliographies  are  appended  to  the 
articles  on  infective  diseases  in  Allbutt's  System  of 
Medicine  (especially  vols.  I.  and  II.).  Muirand  Ritchie's 
excellent  Manual  of  Bacteriology  also  contains  refer- 
ences to  many  of  the  more  important  papers  on  special 
topics. 


INDEX. 


Abrin,  321,  329,  385,  387. 

Actinomyces,  42,  56,  143,  205 
note. 

Actinomycosis,  204. 

Active  Proteids,  48,  49,  86,  93, 
98,  118-125,  309,  310,  360. 

Adaptation,  56. 

Aerobiosis,  56,  62,  96. 

Alcohol  (misuse  of),  411. 

Alcoholic  fermentation,  57,  59, 
207  ; of  milk,  117. 

Alexins,  357 — 377.  See  Active 
proteids. 

Alternation  of  generations,  270, 
271. 

Amrebae,  208. 

Anaerobiosis,  50-60,  96,  97,  178, 
180. 

Animal  parasites.  See  Para- 
sites. 

Anthrax,  156-160,  261,  266,  302, 
308,  377,  390 ;  Bacillus  of 
— ,  see  B.  anthracis  ;  cu- 
taneous   ,  318  ;  intestinal 

,  318  ;  symptomatic , 

see  Symptomatic  anthrax. 

Antidotes,    286,    287,    321,    323, 

329-33I- 

Antisepsis,  68,  72,  430. 
'  'Anti-substance. "  See  Antidote. 


Antitoxin,  327-397  ;  diphtheria 
.  See  Diphtheria. 

Anti-venin,  385,  388. 

Arrack  fermentation,  45. 

Arsenic,  393. 

Arthrobacterium,  35,  38,  195. 

Arthrospores,  12,  14,  27-31,  36- 
40,  185,  365 

Ascococcus,  16,  18. 

Asepsis,  71. 

Aseptol,  76. 

Asparagin,  97,  98. 

Aspergillus,  Oryzae,  116. 

Attenuation,   58,  60,  61,  66,  69. 

Bacillus,  23,  35,  38 ;  an- 
thracis, 19,  30,  33-35,  45,  66, 
82,  (spores  of,  69,  72,  90), 

138,   156-160,  261,  266  ;  

coli  communis,  140,  174,  190, 

192,    193,    257 ;    crassus 

sputigenus,  172  ;  icteroi- 

des,  215  ;   megatherium, 

30  ;   mesentericus,    127  ; 

—  prodigiosus,  131,  140,152; 

—  proteus,    149,    150;  - 

pyocyaneus,i5o,i5i,377; 

Solmsii,  32  ; subtilis,  19, 

25,  30,  31.  67,  127. 

Bacteriaceae,  38. 


462 


INDEX. 


Bacterial  forms,  10-13. 

Bacterium,  23,  35  ;  capsu- 

latum  pneumoniae,  172  ; 

chlorinum,  61 ; paludo- 

sum,  32  ;  pediculatum,  45  ; 

photometricum,  61 ;  ter- 

mo,  25,  127,  130; Zopfii, 

12,  19,  31. 

Beggiatoa,  18,  38,  40,  63,  in, 
112. 

Black  Death,  243. 

Black-leg,  181. 

Blenorrhoea,  177. 

Blood,    bactericidal   power    of, 

359- 

Bothriocephalus  latus,  270. 
Branching,  43,  44. 
Bubonic  plague,  195. 
Building  laws,  420. 

Capsulated  bacteria,  172,  173. 

Carbolic  acid,  72,  73,  76-78,  83, 
88,  90,  432. 

Cause,  definition  of  term,  230. 

Cell-division,  6,  26. 

Cell-membrane,  4,  6. 

Cells,  structure  of,  3-6. 

Cerebro-spinal  meningitis,    174. 

Cheese  bacteria,  136. 

Chicken  cholera,  162,  300,  319. 

Chlamydospores,  29,  34,  43. 

Chlorine,  72,  73. 

Chlorophyl,  61,  62,  91,  103,107, 
108. 

Cholera  asiatica,  184-191,  243, 
268,  301,  307.317.322-324,339, 
390,  398,  399,  411,  425,  426, 
(Hamburg  epidemic,  412,  414, 

423.  435):  poisons  of  , 

123,  385;  bacteria  of ,  19, 

25.  36,  43.  57.  58,  60,  69,  75, 


130,  140,  401;  cholera-red  re- 
action, 188,  189. 
Cholera  nostras,  190. 
Cholin,  120,  121. 
Chromatium,  7,  8. 
Chromulina,  34 
Chrysomyxa  rhododendri,  245  ; 

ledi,  245. 
Cilia,  24-26. 
Cinnamic  acid,  392. 
Cladothrix,  7,   8,  15,  38,  40,  42, 

44-46,  186. 

Classification,  10,  u,  36-41. 
Clathrocystis,  16,  18. 
Cleanliness,  419,  430-432;  teach- 
ing of ,  413,  414. 

Clostridium,    9,    19,   30-32,   35, 

38,  180. 
Coal   formation,    beginning   of, 

ii2,  113,  130. 
Coccaceae,  37. 
Coccobacteria  septica,  138 
Colon  bacillus.   See  B.  coli  com- 

munis. 

Colonies  of  bacteria,  13,  14,  16. 
Comma  bacilli,   20,   31,   36,  43, 

60,   184,   185,    189,    301,    324, 

344.  426. 
Constancy,  of  form,  21,  22,  23, 

126,  139-144  ;  of  species 

126,  137,  138. 
Cordyceps,  244. 
Corrosive  sublimate,  72,  73,  75, 

76.  432- 
Cow-pox,  299. 
Creatin,  392 
Crenothrix,    28,    38,    40 ;    

ochracea,  in. 
Creolin,  78. 
Cresol,  77-79.  85. 
Cyanophyceae,  39,  41,  64. 


INDEX. 


463 


Cycle  of  activity,  254.  264. 
Cystopus  candidus,  245. 

Degeneration  forms,  19. 

Deutoplasm,  4. 

Diphtheria,    182,   307,  317,  318, 

327.  337)  bacillus  of ,  34, 

35,    43,    263,    293,    325;  - 
serum,  349,  350,  352-356,  386, 
387; toxin,  123,  182,  316, 

385- 

Diplococcus,  intracellularis,  174; 

lanceolatus,  171.  See 

Pneumonia,  172,  344. 

Discontinuous  sterilization,  68, 
69. 

Disease,  a  process,  224  ;  para- 
sitic theory  of  ,  227  ; 

Schleich's  description  of , 

404  ;  stimuli,  251-272. 

Disinfectants,  71-84. 

Disinfection,    68,     71-90,     430- 

432  ;  nuisance,  424  ;  ab- 
surdity of ,  427-429;  — 

of  body,  432  ;  of  linen, 

433  ;  of   sick-room,    433, 

434- 

Disintegration,  20. 

Dissemination  of  disease  germs, 
422,  425. 

Distomum  hepaticum,  270. 

Division  of  cells,  6. 

Drinking  too  much,  408,  409. 

Drying,  behavior  of  bacteria  to- 
wards, 69,  131,  171;  behavior 
of  active  proteids  towards,  88. 

Dysentery,  208. 


Echinococci,  270. 
Education,    hygienic. 
gienic  education.  ' 


See  Hy- 


Electricity,  effect  of,  upon  bac- 
teria, 70,  71. 

Emulsin,  391. 

Endospores,  29-35,  39.  4°.  42, 
64-66. 

Energy,  relations  of  bacteria  to, 

52-55- 
Enzymes,  46,  65,  72,  87,  88,  125, 

328. 
Erysipelas,  swine,  160,  161,  302, 

339,    417  ;    bacteria  of , 

263,  303. 

Fermentation,  17-19,  46,  48,  57, 
59,  70,  128,  129;  lactic  acid 

— .  134- 
Ferments,    digestive,    306,    336, 

390  ;  lifeless ,  47,  48,  87. 

Fever,  60,  153,  382. 
Flagella,  24-26. 
Florid  children,  407. 
Fluorescence,  63. 
Formaldehyde,  94,  95,  97,    104, 

107,  109. 

Form-genera,  34,  35,  126. 
Form-species,  34,  35,  126. 
Forms  of  bacteria,  10,  u. 
Friedlander's  bacillus,  172. 

Glanders,  206 ;  bacillus  of , 

3i3- 

Gonidia,  27,  28. 
Gonorrhoea,  177,  Fig.  25,  p.  161. 
Granules,  3,  4,  26. 
Gregarinidae,  176. 

Hay  bacillus,  67,  127,  130,  134, 

152. 

Hydration,  52. 
Hydrophobia,  315,  318.     See 

Rabies. 


464 


INDEX. 


Hygiene,  405,  406,  412,  421. 
Hygienic  education,  413-416. 
Hyperaemia,  392. 

Immunity,  218,  243,  Chap.  VI.; 

active  and  passive ,  316- 

327»  373  >  natural  and  ac- 
quired   ,  314-316,  374- 

391;  influence  of  nourishment 
upon ,  394. 

Immunizing  proteids,  332,  362. 

Inflammation,  391,  392. 

Influenza,  174. 

Iodine  terchloride,  393,  394. 

Iron  algae,  in. 

Iron  bacteria,  in,  115.  See 
Crenothrix  ochracea  and 
Leptothrix  ochracea. 

Isolation  of  sick,  435,  436. 

Isopathy,  389. 

Laboulbenia  muscae,  244. 
Lepidium  sativum,  245. 
Leprosy,  202. 
Leptothrix,    9,     38,     42  ;    

ochracea,  in. 
Leucocytes,  361-367,  391. 
Leucocytosis,  390. 
Leuconostoc,  14,  31,  40. 
Light,    behavior    towards,    61, 

107. 

Lime,  milk  of,  432. 
Lockjaw,  177. 
Luminous  bacteria,  62,  63. 
Lysol,  78,  79. 

Macrophages,  176. 

Malaria,  210-212,  279-291,  393. 

Malignant   oedema,    179-181, 

307- 
Mallein,  312-314. 


Meningitis,  174. 

Merista,  170. 

Metabiosis,  117. 

Micrococcus,  23,  37  ;  amy- 

lovorus,  209 ;  prodi- 

giosus,  26  ;  tetragenus, 

170; phosphorescens,  63. 

Milk,  sterilization  of,  68,  69. 

Motility,  24,  26. 

Moulds,  212-214,  267. 

Mouse  typhoid.     See  Typhoid. 

Mucor,  29,  116,  214. 

Myconostoc,  14. 

Myxomycetes,  208. 

Nitrification,   57,  109,  110,  428. 
Nomenclature,  23,  36-41. 
Normal  serum,  326. 
Nostoc,  40. 
Nucleus,  4,  6-8. 

CEco-parasites,    169,    171,    184, 

190,  193. 
CEdema,    malignant,     179-181, 

307- 

Oscillaria,  40. 
Overfeeding,  407-409. 
Oxidation,   53,  55-60,   97,    109, 

112. 
Oxygen,  behavior  towards,  60, 

61.     See  Anaerobiosis,  62. 
Ozaena,  173. 

Paraplasm,  4. 

Parasites,  animal,  176,  269 ; 

facultative  ,  255,  256, 

269;  obligatory ,  255;  de- 
velopment of  ,  403  ;  in- 
fluence of  sanitation  upon 
,  400,  401  ;  strict  and  oc- 
casional   ,  400. 


INDEX. 


465 


Parasitic  theory  of  disease.  See 

Disease. 
Pasteuria,  17. 
Pasteurization,  69. 
Perlsucht,  201,  207. 
Phenol,  77,  78,  80,  81. 
Phosphorescence,  62. 
Phragmidiothrix,   38. 
Phytophtora  infestans,    244  ; 

omnivora,  244. 

Pigments,   bacterial,  61-63,  9^- 
Plasmodiophora  brassicae,  209. 
Plasmodium  malariae,  210. 
Plasmolysis,  8,  9. 
Plectridium,  30,  35,  38,  178. 
Pleomorphism,  43,  44,  46. 
Pneumonia,  339,  344,  390 ;  bac- 
.    teria  of ,  61,  170,  171,  263. 
Poisons,  bacterial,   58,  89,  118- 

125- 

Polymerization,  51,  52. 
Potato  bacillus,  25,  67,  127,  134 
Predisposition  to   disease,  242, 

266,  295,  401,  404,  406,  414, 

4J5- 

Protective  inoculation,  389-390 
Proteids,  306,  343;  active,  48,  49, 

86,  93,  360  ;  passive,  123,  124. 
Proteus,  25,  149,  150,  307. 
Protoplasm,  structure  of,  3,  4. 
Protozoa,  209. 
Prussic  acid,  81,  92. 
Pseudo-diphtheria  bacillus,  184. 
Pseudo-tuberculosis,  201. 
Pseudo-influenza  bacillus,  175. 
Ptomaines,  118-122,  306. 
Pure  cultures,  21,  66,  67. 
Pyaemia,    156,    160,    167,     173 ; 

— -  staphylococci,  317. 
Pyocyaneus,   150,  307.     See  B. 

$yocyaneus. 


Pyogenic  bacteria,  166-170. 
Pythium,  244. 

Quinine,  72,  279-284,  393. 

Rabies,  303.   See  Hydrophobia. 
Reduction,  51,  53. 
Relapsing  fever,  175. 
Relationship  of  bacteria,  40,  41. 
Resistance  to  disease,  260,  266, 

401,  404,  409. 
Rhinoscleroma,  172. 
Ricin,  321,  329. 

Saccharomyces,  40,  207. 

Salicylic  acid,  80. 

Salicylicates,  279,  280. 

Sanitation,  399-402,  425,  426 ; 

works  of  ,  413,  418,  424, 

427,  428,  438,  439. 

Sapocarbol,  78. 

Saprolegnia,  176. 

Saprophytes,  258,  401,  428 ; 
facultative  ,  255 ;  occa- 
sional   ,  400. 

Sarcina,  16,  18,  37;  sep- 

tica,  170, 

Scarlet  fever,  436. 

Schizophytes,  40-42. 

Sclerothrix,  42. 

Sclerotinia,  244. 

Scorpion-venom,  386. 

Septicaemia,  160,  167,  171,  172, 

208,  210  ;  haemorrhagic , 

162; of  carp,  176;  mouse 

,  160,  161  ;  rabbit  , 

318,  391 ;  Vibrio ,  307. 

Serum,  normal,  326,  384  ;  cura- 
tive   ,  383,  387,  388;  diph- 
theria  ,  see  Diphtheria. 


466 


INDEX. 


Small-pox,  243,  244,  296-299. 

Snake-blood,  338. 

Snake-venom,     329,    338,    385- 
388. 

Sodium    cresotinate,    79 ;    

salicylicate,  79. 

Soil,  bacteria  in,  64,  425,  426. 

Solutol,  79,  432. 

Solveole,  79,  432. 

Spirillum,    23,    35,    36,    38,    58, 

59 ; amyliferum,     30 ; 

desulfuricans,  112;  

rubrum,    56; serpens, 

25,  30 ;  undula,  7,  8,  9, 

10,  29. 

Spirobacteriaceae,  38. 

Spirochsete,    15,  20,   23,   35,  36, 

38  ;  of  relapsing  fever, 

175,  1 86. 

Spontaneous  generation,  46-49 

Spore-formation,  26-35. 

Spores,  behavior  of  to  temper- 
ature, 64-67. 

Staphylococcus,   16,    170 ;  

pypgenes    aureus,     139,    166, 
167  ;  pyaemia,  385. 

Sterilization,    67-69 ;     of 

milk,  132,  133. 

Stimulus,    to     protoplasm,    90, 

280-287,    290  ;    disease   , 

'see   Disease;     Specific   stim- 
uli, 389,  395.  396. 

Streptococcus,     37,     357,     386  ; 

pyogenes  or  erysipelatos, 

167-170. 

Strychnine,  393. 

Sulphur     bacteria,      in.      See 
Beggiatoa,  115. 

Suppuration,    262,   263.     See 
Pyogenic  Bacteria. 

Surra,  209. 


Susceptibility    to   disease,    147, 

169,  243,  244. 
Swine,     diseases    of,     162-166 ; 

plague,  339; plague 

bacillus,  25. 
Symbiosis,  115-117. 
Symptomatic  anthrax,  181,  182, 

302,  307,  417;  bacillus  of , 

57-  66. 
Syphilis,  203,  204. 

Taeniae,  176. 

Taenia  solium,  270  ; medio- 

canellata,  270. 

Temperature,  behavior  towards, 

63-70,  85,  86  ;  rise  of , 

382. 

Terminology,  235. 

Tetanus,  317,  318,  327,  329,  330, 

337,  358  ;  bacteria,  30, 

177  ;  -  -  toxin,  123,  179, 

315,  316,  327,  328,  385  ;  

serum,  351. 

Teukrin,  392. 

Thiosinamin,   392. 

Thrush,  213. 

Thymus,  390. 

Transmission  of  acquired  char- 
acters, 246-248. 

Tubercles  of  Leguminosae,  bac- 
teria in,  115. 

Tuberculin,  312-314,  344,  350, 
380,  392. 

Tuberculosis,  197,  243,  278, 
313,  392,  402  ;  bacillus  of 

— -  34-  35.  42.  43.  ii3,  MS. 

198,  263  ;  miliary ,  207  ; 

peritoneal ,  392. 

Typhoid  fever,  191,    380  ;  

bacteria,     25,    34,    328,    344  ; 
serum,    356,    380,    381  ; 


INDEX. 


467 


-    toxin,    385  ;    mouse    ty- 
phoid, 196. 

Jredineae,  271. 
Urschleim,  4. 
Ustilagineae,  271. 

Vaccination,  298,  299,  416,  417. 
Vacuoles,  4,  6. 
Variability,  21-23. 
Vibrio,    23,    35,    36,    38  ;    - 
cholerae  asiaticse,    19,   25,  36, 


—  rugula,  19,  29,  30  ; 

septicaemia,  307. 
Virulence,   diminution   of,    301, 

427. 

Water,  bacteria  in,  63,  64. 
Water-supply,  419,  420,  423. 

Yeasts,  116,  117,  127. 
Yellow  fever,  215,  243. 

Zoogloea,  14,  20,  21  ;  ram- 

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books  published  by  The  Open  Court  Publishing  Company.  Yearly,  $1.50 
Separate  copies  according  to  prices  quoted.  The  books  are  printed  upon 
good  paper,  from  large  type. 

The  Religion  of  Science  Library,  by  its  extraordinarily  reasonable  price, 
will  place  a  large  number  of  valuable  books  within  the  reach  of  all  readers 

The  following  have  already  appeared  in  the  series: 

No.  i.   The  Religion  of  Science.     By  PAUL  CARUS.     250. 

2.  Three  Introductory  Lectures  on  the  Science  of  Thought.     By  F.  MAX 

MULLER.     250. 

3.  Three  Lectures  on  the  Science  of  Language.     By  F.  MAX  MOLLER.     250. 

4.  The  Diseases  of  Personality.     By  TH.  RIBOT.     250. 

5.  The  Psychology  of  Attention.     By  TH.  RIBOT.     250. 

6.  The  Psychic  Life  of  Micro-  Organisms.     By  ALFRED  BINET.     250. 

7.  The  Nature  of  the  State.     By  PAUL  CARUS.     150. 

8.  On  Double  Consciousness.     By  ALFRED  BINET.     150. 

9.  Fundamental  Problems.     By  PAUL  CARUS.     5oc. 

10.  >  The  Diseases  of  the  Will.     By  TH.  RIBOT.     250. 

11.  The  Origin  of  Language.     By  LUDWIG  NOIRE.     150. 

12.  The  Free  Trade  Struggle  in  England.     By  M.  M.  TRUMBULL.     250. 

13.  Wheelbarrow  on  the  Labor  Question.     By  M.  M.  TRUMBULL.     350. 

14.  The  Gospel  of  Buddha.     By  PAUL  CARUS.     350. 

15.  The  Primer  of  Philosophy.     By  PAUL  CARUS.    250. 

16.  On  Memory \  and  The  Specific  Energies  of  the  Nervous  System.     By  PROF 

EWALD  HERING.     150. 

17.  The  Redemption  of  the  Brahman.     ATale  of  Hindu  Life.     By  RICHARD 

GARBE.    250. 

18.  An  Examination  of  Weismannism.     By  G.  J.  ROMANES.     350. 

19.  On  Germinal  Selection.     By  AUGUST  WEISMANN.     250. 

20.  Lovers  Three  Thousand  Years  Ago.     By  T.  A.  GoorwiN.     150. 

21.  Popular  Scientific  Lectures.     By  ERNEST  MACH.     500. 

22.  Ancient  India  :  Its  Language  and  Religions.     By  H.  OLDENBERG.     250 

23.  The  Prophets  of  Ancient  Israel.     By  PROF.  C.  H.  CORNILL.     250. 
•it,.  Homilies  of  Science.     By  PAUL  CARUS.     350. 

25.  Thoughts  on  Religion.     By  G.  J.  ROMANES.     50  cents. 

26.  The  Philosophy  of  Ancient  India.     By  PROF.  RICHARD  GARBE. 

27.  Martin  Luther.     By  GUSTAV  FREYTAG.     350. 

28.  English  Secularism.     By  GEORGE  JACOB  HOLYOAKE.     250. 

29.  On  Orthogenesis.     By  TH.  EIMER.     250. 

30.  Chinese  Philosophy.     By  PAUL  CARUS.     250. 

31.  The  Lost  Manuscript.    By  GUSTAV  FREYTAG.    6oc. 

32.  A  Mechanico-Physiological  Theory  of  Organic  Evolution.     ByCARLVON 

NAEGELI.    150. 

THE  OPEN  COURT  PUBLISHING   CO. 

324  DEARBORN  STREET,  CHICAGO,  ILL. 
LONDON:  Kegan  Paul,  Trench,  Trubner  &  Co. 


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